Dialysis and methods including sensor feedback to improve patient experience

ABSTRACT

Peritoneal dialysis, such as automated peritoneal dialysis (“APD”) is provided with any one or more or all of the following sensing or feedback features: impedance sensing to detect peritonitis, temperature sensing to detect peritonitis, bio-MEMS sensing to detect peritonitis, and glucose control for diabetes patients, wherein each sensing or feedback feature analyzes patient effluent fluid or fluid dwelling within a patient&#39;s peritoneal cavity.

PRIORITY CLAIM

This application is a non-provisional application claiming priority toand the benefit of provisional U.S. Patent Application No. 62/703,749,filed Jul. 26, 2018, entitled “Dialysis Systems And Methods IncludingSensor Feedback To Improve Patient Experience”, the entire contents ofwhich are incorporated herein by reference and relied upon.

BACKGROUND

The present disclosure relates generally to the treatment of end stagerenal disease. More specifically, the present disclosure relates tomethods and apparatuses for monitoring and/or controlling theperformance of peritoneal dialysis.

Using dialysis to support a patient whose renal function has decreasedto the point where the kidneys no longer sufficiently function is known.Two principal dialysis methods are provided, namely, hemodialysis; andperitoneal dialysis.

In hemodialysis, the patient's blood is passed through an artificialkidney dialysis machine. A membrane in the machine acts as an artificialkidney for cleansing the blood. Because it is an extracorporealtreatment requiring special machinery, certain inherent disadvantagesexist with hemodialysis. To overcome disadvantages associated withhemodialysis, peritoneal dialysis has been developed. Peritonealdialysis uses the patient's own peritoneum as a semi-permeable membrane.The peritoneum is a membranous lining of the patient's abdominal bodycavity. Due to good perfusion, the peritoneum acts as a naturalsemi-permeable membrane.

Peritoneal dialysis periodically infuses a sterile aqueous solution ordialysis fluid into the peritoneal cavity. Diffusion and osmoticexchanges take place between the peritoneal dialysis fluid and the bloodstream across the natural body membranes. The exchanges remove the wasteproducts that the kidneys normally excrete. The waste products consistof solutes like urea and creatinine. The kidneys also maintain thelevels of other substances such as sodium and water. Dialysis regulatesthe diffusion of water and solutes across the peritoneal membrane duringdialysis, which is called ultrafiltration.

In continuous ambulatory peritoneal dialysis (“CAPD”), a dialysissolution is introduced into the peritoneal cavity via a catheter. Anexchange of solutes between the dialysis fluid and the blood is achievedby diffusion. Further solute removal is achieved via the dialysis fluidproviding a suitable osmotic gradient from the blood to the dialysisfluid. The osmotic gradient allows a proper acid-base, electrolyte andfluid balance to be achieved in the patient's body. Used dialysis fluidor effluent fluid is drained manually via gravity from the body cavitythrough the catheter.

A variation of CAPD is automated peritoneal dialysis (“APD”). APD uses amachine, called a cycler, to automatically infuse, dwell, and drainperitoneal dialysis fluid to and from the patient's peritoneal cavity.APD is attractive to a peritoneal dialysis patient because it may beperformed at night while the patient is asleep, which frees the patientfrom the day-to-day demands of CAPD during his/her waking and workinghours.

The APD sequence typically lasts for several hours. It often begins withan initial drain phase to empty the peritoneal cavity of spent dialysisfluid from the prior treatment. The APD sequence then proceeds through asuccession of fill, dwell, and drain phases that follow one after theother. Each fill/dwell/drain sequence is called a cycle.

The proportion of patients performing automated peritoneal dialysis(“APD”) is increasing worldwide, which is due in part to the ability ofAPD to be adapted to the patient's particular needs regarding thepatient's private life and the patient's therapy needs. The two primarygoals of dialysis, solute clearance and ultrafiltration (“UF”) depend onthe modality or type of APD performed (e.g., nocturnal intermittentperitoneal dialysis (“NIPD”), continuous cycling peritoneal dialysis(“CCPD”) and hi-dose CCPD), the solution type, the therapy time and thefill volume. Prescribing an APD therapy constitutes selecting one ofeach of these. Thus there are many combinations and possibilities fromwhich to choose.

APD devices typically do not have the capability to provide feedback tothe patient regarding the effectiveness of his/her recent therapies.Also, APD devices typically run open loop such that they do not adjusttherapy parameters (e.g., modality, solution type, therapy time and fillvolume) based on the actual measured daily clearance and UF.Accordingly, some patients underachieve their targets and developadverse conditions such as fluid overload and in some caseshypertension. Current methods for adjusting treatment typically involvethe patient reporting to a center every so often to be evaluated. Thesemethods place the burden of therapy adjustment solely on the doctor orclinician and do not occur frequently enough to adjust properly to thepatient's weekly, monthly, seasonal or other lifestyle change.

APD, like CAPD, uses a catheter implanted in the patient's peritoneum todeliver fresh dialysis fluid to and to remove used dialysis fluid fromthe patient's peritoneal cavity. The placement of the peritonealcatheter provides an opportunity to sense desired parameters within thepatient. Additionally, APD and CAPD both remove used or effluent PDfluid from the patient, which provides opportunities to sense patientparameters or characteristics residing within the effluent fluid. A needaccordingly exists to provide systems and methods that take advantage ofthe placement of the patient catheter and/or the effluent PD fluidremoved from the patient to help monitor and/or control a peritonealdialysis treatment, such as CAPD and APD. And more generally, a needexists for immediate or in-treatment feedback to help with variousproblems associated with peritoneal dialysis.

SUMMARY

The examples described herein disclose systems and methods for improvedperitoneal dialysis (“PD”) treatment. Three of the systems and methodsdescribed herein involve detection and optimally early detection ofperitonitis. Peritonitis is an inflammation of the peritoneum, which isthe tissue that lines the inner wall of the abdomen and covers andsupports most of the abdominal organs. The peritoneal wall is also themembrane used for peritoneal dialysis as described above. Peritonitis isusually caused by infection from bacteria or fungi, which may enterthrough the patient's peritoneal catheter.

Left untreated, peritonitis can rapidly spread into the blood (sepsis)and other organs, resulting in multiple organ failure and death. Thefirst symptoms of peritonitis are typically poor appetite and nausea anda dull abdominal ache that quickly turns into persistent, severeabdominal pain. Other signs and symptoms related to peritonitis mayinclude: abdominal tenderness or distention, chills, fever, fluid in theabdomen, and vomiting.

The death rate from peritonitis depends on many factors, but can be ashigh as 40% in those who also have cirrhosis. As many as 10% may diefrom secondary peritonitis. Primary spontaneous peritonitis is aninfection that develops in the peritoneum and is the type associatedwith peritoneal dialysis treatment. Secondary peritonitis usuallydevelops when an injury or infection in the abdominal cavity allowsinfectious organisms into the peritoneum. Both types of peritonitis arelife-threatening.

Current methods for determining peritonitis are subjective and place theburden on the patient. For example, patients may be told to observe thecolor and/or texture of their effluent fluid to look for peritonitis.Or, patients may be told to be aware of a full stomach feeling and/orfever. When the patient thinks peritonitis is oncoming or present, thepatient has to bring an effluent sample to the clinic for testing. Theabove methods are subjective and place the burden on the patient. Thebelow systems and methods are automatic and objective.

Temperature Sensing for Peritonitis

In one primary embodiment, the temperature of used dialysis fluidexiting the patient is measured to detect peritonitis. In healthypatients, the temperature of used dialysis fluid is normal bodytemperature or about 37° C. In patients experiencing the onset ofperitonitis, the used dialysis fluid exiting the patient may reside atan elevated temperature. The system and method of the first primaryembodiment measure the effluent dialysis fluid and use the measurementto make a determination as to whether the patient may be experiencingthe onset of peritonitis.

The temperature measurement may be made in a number of different ways.In one way, a temperature sensor, such as a thermocouple or thermistoris placed in a connector, such as a clamshell type connector, whichclips removeably and selectively over the patient line. The clamshellconnector may be placed in any desired location around the patient line,for example, near the patient so that the temperature of the patient'seffluent dialysis fluid may be taken immediately upon leaving thepatient. In one embodiment, the temperature of the effluent fluid iscompared to the temperature of the fresh dialysis fluid, which may beheated to body temperature or 37° C. In this manner, any temperatureoffset caused by the generally non-thermally conductive tubing isnegated. For example, if the temperature of the 37° C. fresh dialysisfluid is read through the tubing at an offset temperature of 32° C., thesame offset will be assumed for the effluent fluid leaving the patient.The control unit reading the temperature signal will therefore look fora 32° C. patient healthy signal and will trigger a potential peritonitisalert when the control unit sees a signal indicating a temperature above32° C.

In an alternative embodiment, a more thermally conductive and medicallysafe material, such as stainless steel is spliced or fitted into thepatient line. One or more thermally conductive electrode is attached tothe temperature sensor and allows for a more accurate temperaturereading. Here, the control unit reading the temperature signal looks inone embodiment for a 37° C. patient healthy signal and triggers apotential peritonitis alert when the control unit sees a signalindicating a temperature above 37° C. In this example, the control unitmay or may not take the incoming temperature of fresh dialysis fluidinto account.

In any embodiment in which the temperature sensor is located remote fromthe cycler, the temperature sensor may send the measured signals in awired or wireless manner to the cycler for interrogation. Thetemperature sensor is in one embodiment a passive device (e.g., twowires creating voltage based upon fluid temperature). If the temperaturesensor does require power, power may be provided via a battery or fromthe cycler or a water purifier operating with the cycler via powerwires.

In a further alternative embodiment, the temperature sensor, e.g.,thermocouple or thermistor, is located within the dialysis machine orcycler and operates with the disposable cassette or the patient lineextending from the disposable cassette. The temperature sensor contactsthe flexible sheeting of the disposable cassette in one or more placesin one embodiment. One or more thermally conductive contact may beformed in or added to the disposable cassette to help temperaturesensing accuracy. As above, when sensing at or near the cassette, thecontrol unit may or may not take the incoming temperature of freshdialysis fluid into account.

Temperature sensing is performed alternatively in a drain line extendingfrom the disposable cassette. The drain line is advantageous becausesterility is less of an issue, such that the drain line is in oneembodiment plugged into a reusable thermally conductive contact providedwith the cycler or with a water purification device operating with thecycler.

The control unit is programmed in one embodiment to alert the patient atthe user interface of the cycler if an elevated temperature indicatingperitonitis is detected. Alternatively or additionally, the control unitoperates via a network and one or more server computer to enable adoctor or clinician to view effluent temperature data, e.g., on anongoing basis, so that the clinician may determine if the patient is atrisk of peritonitis. The data is displayed in one embodiment on adashboard of a website for the patient, wherein the temperature data maybe presented with a flag for the clinician when it is elevated,indicating peritonitis.

Bio-MEMS Sensing for Peritonitis

In a second primary embodiment, which may be used alternatively or inaddition to the first embodiment, a bio-Micro-Electro-Mechanical-System(“bio-MEMS”) sensor is used to detect peritonitis. The bio-MEMS sensoris used to look for the presence of white blood cells from the patientin the effluent, which is an indicator of peritonitis. In oneimplementation, effluent fluid from the cycler is pumped to drain. Thedrain line is connected to a lab-on-chip diagnostic detection device.The lab-on-chip or bio-MEMS device includes a container into which asampling line extends, wherein the sampling line may extend or tee offof the drain line. The effluent sample entering the container of thebio-MEMS device first encounters a microfluidic pathway that splits thepatient's white blood cells from the effluent fluid. The white bloodcells are then weighed using a piezoelectric biosensor in oneembodiment. The piezoelectric biosensor resonates with a frequencyproportional to a change in the deposition rate of white blood cells.

The bio-MEMS device is placed alternatively in the patient line via asample line and used to analyze effluent returning from the patient. Inthis manner, the bio-MEMS device may be used to sense fresh dialysisfluid delivered to the patient additionally if desired.

In one embodiment, the bio-MEMS device includes the electronics andprocessing to process raw signals from the piezoelectric biosensor andmake a determination as to the presence or not of white blood cells. Thebio-MEMS device may also include a user interface to indicate to thepatient or caregiver present during treatment weather or not there is anindication of peritonitis. In an alternative embodiment, either one orboth of (i) electronics and processing to process raw signals from thepiezoelectric biosensor or (ii) the user interface for patient orcaregiver communication may be provided instead by the cycler or perhapsa water purification device operable with the cycler.

As with the first primary embodiment, the control unit and processingfor the second primary embodiment may alternatively or additionallyoperate via a network and one or more server computer to enable a doctoror clinician to view bio-MEMS data, e.g., on an ongoing basis, so thatthe clinician may determine if the patient is at risk of peritonitis.The data of the second primary embodiment may be displayed incombination with the data of the first primary embodiment to provide acombination of peritonitis indicators.

Impedance Monitoring for Peritonitis

In a third primary embodiment, which may be used alternatively or inaddition to the first embodiment and/or the second embodiment, animpedance monitor is used to detect peritonitis. The impedance monitoris used to look for the presence of white blood cells from the patientin the effluent fluid, which again is an indicator of peritonitis. Invarious implementations, the impedance monitor may be placed anywherethat the patient's effluent fluid may be sensed, for example, in thepatient's indwelling catheter, along the patient line or anywhere alongthe drain line. In any of these locations, the catheter or line isfitted with electrodes, e.g., in any of the ways discussed above fortemperature sensing, but with the goal now of placing electricallyconductive contacts in communication with the effluent dialysis fluid.

An electrically conductive and medically safe material, such asstainless steel, is spliced or fitted into the catheter, patient line ordrain line in one embodiment, e.g., via a clamshell connector or aconnector that is spliced into the drain line. The control unitcontrolling the impedance monitor in one embodiment causes an electricalfrequency sweep to be generated in the effluent fluid. Such impedancespectroscopy (or obtaining complex impedance) may provide additionaldetails about the content(s) of the effluent fluid. For example, theelectrical properties of fibrin (normal, not indicating peritonitis) mayvary from the electrical properties of white blood cells (indicatingperitonitis). Once the electrical properties of different substanceswithin the effluent fluid are learned, the properties may be programmedinto the control unit and used thereafter to determine what if anythingis entrained in the effluent dialysate stream.

In any embodiment in which the impedance monitor is located remote fromthe cycler, the impedance monitor may send the measured signals in awired or wireless manner to the cycler for interrogation. The impedancemonitor as mentioned above has the ability to emit a frequency sweepinto the effluent fluid and thus may receive power either via a batteryor from the cycler or a water purifier operating with the cycler viapower wires.

In an alternative embodiment, the impedance monitor is located withinthe dialysis machine or cycler and operates with the disposable cassetteor the patient or drain line extending from the disposable cassette. Theimpedance monitor extends through a rigid wall holding the disposablecassette sheeting in one or more places in one embodiment. In a furtheralternative embodiment, the impedance monitor is operable with the drainline located within a water purifier supplying purified water to thedialysis machine or cycler.

The control unit is programmed in one embodiment to alert the patient orcaregiver at the user interface of the cycler if white blood cellsindicating peritonitis are detected. Alternatively or additionally, thecontrol unit operates via a network and one or more server computer toenable a doctor or clinician to view effluent impedance data, e.g., onan ongoing basis, so that the clinician may determine if the patient isat risk of peritonitis. The data is displayed in one embodiment on adashboard of a website for the patient, wherein the effluent impedancedata may be presented with a flag for the clinician when white bloodcells are present, indicating peritonitis. The data of the third primaryembodiment may be displayed in combination with the data of the firstand/or second primary embodiments to provide a combination ofperitonitis indicators.

When the impedance monitor is placed in the indwelling catheter or inthe patient line via a sample line and used to analyze effluent withinthe patient or returning from the patient, the impedance monitor may beused to sense fresh dialysis fluid delivered to the patient additionallyif desired. When the impedance monitor is placed in the drain line, itmay be used additionally to detect if dialysis fluid made at the pointof use has been mixed properly.

Glucose Control for Diabetic Patients

Glucose (or dextrose) is the primary osmotic agent used with most PDsolutions. The absorption of most of the peritoneal glucose load over adwell period may have a detrimental effect on patients suffering fromdiabetes. Diabetes is a common cause of kidney failure leading to theneed for dialysis treatment. In addition, daily exposure to glucose mayinduce hyperglycemia in PD patients, which can have seriousconsequences. Certain diabetic PD patients accordingly receive insulinwith their PD treatment to help maintain a glucose balance. Patientsreceiving insulin with PD treatment, however, run the risk of trying tomatch the amount of insulin to the amount of PD treatment received.

In a fourth primary embodiment, which may be used alternatively or inaddition to the first, second and/or third primary embodiments, abio-MEMS-insulin system and method are provided to match the amount ofinsulin to the amount of PD fluid used. The bio-MEMS-insulin system andmethod measures the glucose level of the effluent dialysis fluid leavingthe patient. That measurement is then used to properly dose the patientwith insulin for the next patient PD fill. In one embodiment, thepatient is full of fluid from the previous treatment when beginning thecurrent treatment. That effluent fluid is removed and at least a portionof which is delivered to a MEMS affinity glucose sensor, which sends asignal to a control unit, which determines how much insulin to deliverto a PD supply volume to form a desired concentration of insulin for theinitial fill. The corresponding amount of insulin is then delivered to aPD fluid supply bag to yield the desired concentration.

The MEMS affinity glucose sensor is used in one embodiment to measureglucose in the drained effluent. In one implementation, effluent fluidfrom the cycler is pumped to drain. The drain line is connectedfluidically to the MEMS affinity glucose sensor. The MEMS affinityglucose sensor includes a container into which a sampling line extends,wherein the sampling line may extend or tee off of the drain line. Theeffluent sample entering the container of the MEMS affinity glucosesensor first encounters a microfluidic pathway that splits the glucosemolecules from the effluent fluid. The glucose molecules are thenweighed using a piezoelectric biosensor in one embodiment. Thepiezoelectric biosensor resonates with a frequency proportional to achange in the deposition rate of glucose molecules. Glucose absorbed atthe end of an nth cycle is calculated using the equation for A_(n)discussed below. To compensate for the absorbed glucose for the nthcycle, the administration of the insulin dosage during the subsequentcycle would be calculated using an equation for I_(n+1) discussed below.

The MEMS affinity glucose sensor in one embodiment includes theelectronics and processing to process raw signals from the piezoelectricbiosensor and make a determination as to the proper concentration ofinsulin to prepare with the PD solution. The MEMS affinity glucosesensor may also include a user interface to indicate to the patient orcaregiver present during treatment that the proper insulin level isbeing determined. In alternative embodiments, either one or both of (i)electronics and processing to process raw signals from the piezoelectricbiosensor or (ii) the user interface for patient or caregivercommunication are provided instead by the cycler or perhaps a waterpurification device operable with the cycler. The PD cycler may operatewith pre-prepared PD dialysis fluid or with PD dialysis fluid preparedat the point of use. With pre-prepared PD dialysis fluid, insulin isadded to a heater bag or to an insulin port on the bag of the solution.With PD dialysis fluid prepared at the point of use, insulin may beadded to the mixed dialysis fluid or to any component thereof (purifiedwater, osmotic agent or electrolyte).

the control unit of the cycler operates via a network and one or moreserver computer in one embodiment to enable a doctor or clinician toview insulin usage data, e.g., on a per-treatment basis, so that theclinician may confirm that insulin is being delivered properly. The datais displayed in one embodiment on a dashboard of a website for thepatient, wherein the insulin volume and concentration with PD fluid maybe viewed. The data of the fourth primary embodiment may be displayed incombination with the data of the first, second and/or third primaryembodiments to provide a desired combination of data.

In light of the disclosure herein and without limiting the disclosure inany way, in a first aspect of the present disclosure, which may becombined with any other aspect listed herein unless specified otherwise,a peritoneal dialysis (“PD”) system includes: a cycler including a pumpactuator and a control unit in operable communication with the pumpactuator; a disposable set including a disposable cassette having a pumpchamber, the disposable cassette sized and arranged to be held by thecycler such that the pump chamber is in operable communication with thepump actuator, the disposable set including a patient line and a drainline extending from the disposable cassette; and a temperature sensoroperably coupled to one of the patient line, drain line or disposablecassette to sense a temperature of effluent PD fluid removed from apatient, the sensed temperature used to form a patient peritonitisdetermination, the control unit configured to communicate theperitonitis determination.

In a second aspect of the present disclosure, which may be combined withany other aspect listed herein unless specified otherwise, the sensedtemperature is sent to the control unit, and wherein the control unit isconfigured to analyze the sensed temperature.

In a third aspect of the present disclosure, which may be combined withthe second aspect in combination with any other aspect listed hereinunless specified otherwise, the sensed temperature is sent to thecontrol unit wired or wirelessly.

In a fourth aspect of the present disclosure, which may be combined withany other aspect listed herein unless specified otherwise, the PD systemincludes a network and at least one doctor or clinician computer incommunication with the control unit via the network, the control unitconfigured to communicate the peritonitis determination to at least oneof a patient or caregiver via a user interface of the cycler or the atleast one doctor or clinician computer via the network.

In a fifth aspect of the present disclosure, which may be combined withany other aspect listed herein unless specified otherwise, the PD systemincludes a water purifier configured to supply purified water to thedisposable set, the water purifier including a water purifier controlunit, wherein the sensed temperature is sent to the water purifiercontrol unit, wherein the water purifier control unit is configured toanalyze the sensed temperature, and wherein the cycler control unit andthe water purifier control unit are in communication to allow the cyclercontrol unit to communicate the peritonitis determination.

In a sixth aspect of the present disclosure, which may be combined withthe fifth aspect in combination with any other aspect listed hereinunless specified otherwise, either the cycler control unit or the waterpurifier control unit is configured to analyze the sensed temperature.

In a seventh aspect of the present disclosure, which may be combinedwith any other aspect listed herein unless specified otherwise, thetemperature sensor is placed in a connector configured to couple to thepatient line or the drain line.

In an eighth aspect of the present disclosure, which may be combinedwith the seventh aspect in combination with any other aspect listedherein unless specified otherwise, the connector is (i) a clamshellconnector that fits around the patient line or the drain line or (ii)configured to be spliced between two sections of the patient line or thedrain line.

In a ninth aspect of the present disclosure, which may be combined withthe seventh aspect in combination with any other aspect listed hereinunless specified otherwise, the connector includes electrodes positionedand arranged to contact (a) effluent fluid flowing through the patientline or the drain line or (b) the patient line or the drain linedirectly.

In a tenth aspect of the present disclosure, which may be combined withthe ninth aspect in combination with any other aspect listed hereinunless specified otherwise, in (b) a thermally conductive segment isspliced between sections of the patient line or the drain line, theconnector connected directly to the thermally conductive segment.

In an eleventh aspect of the present disclosure, which may be combinedwith the ninth aspect in combination with any other aspect listed hereinunless specified otherwise, the connector includes leads extending fromthe electrodes to (i) the control unit, (ii) a control unit of a waterpurifier configured to supply purified water to the disposable set, or(iii) a wireless module provided with the connector.

In a twelfth aspect of the present disclosure, which may be combinedwith any other aspect listed herein unless specified otherwise, the PDsystem is configured to analyze the sensed temperature of the effluentPD fluid removed from the patient by comparing the sensed temperature toa temperature of fresh PD fluid delivered to the patient and sensed bythe temperature sensor.

In a thirteenth aspect of the present disclosure, which may be combinedwith any other aspect listed herein unless specified otherwise, the PDsystem is configured to analyze the sensed temperature of the effluentPD fluid removed from the patient by looking for an increase intemperature due to peritonitis or the onset thereof.

In a fourteenth aspect of the present disclosure, which may be combinedwith the thirteenth aspect in combination with any other aspect listedherein unless specified otherwise, the increase in temperature due toperitonitis or the onset thereof is detectable regardless of whether thesensed temperature is offset due to sensing through the patient line,the drain line or the disposable cassette.

In a fifteenth aspect of the present disclosure, which may be combinedwith any other aspect listed herein unless specified otherwise, theperitonitis determination is a first peritonitis indicator, and whichincludes at least one different peritonitis indicator useable incombination with the first peritonitis indicator to form an overallperitonitis determination.

In a sixteenth aspect of the present disclosure, which may be combinedwith the fifteenth aspect in combination with any other aspect listedherein unless specified otherwise, the at least one differentperitonitis indicator useable in combination with the first peritonitisindicator is obtained from at least one of a white blood cell biosensoror a white blood cell impedance sensor.

In a seventeenth aspect of the present disclosure, which may be combinedwith any other aspect listed herein unless specified otherwise, theperitonitis determination is provided in combination with insulininjection made using feedback from a patient effluent glucose biosensor.

In an eighteenth aspect of the present disclosure, which may be combinedwith any other aspect listed herein unless specified otherwise, aperitoneal dialysis (“PD”) system includes: a cycler including a pumpactuator and a control unit in operable communication with the pumpactuator; a disposable set including a disposable cassette having a pumpchamber, the disposable cassette sized and arranged to be held by thecycler such that the pump chamber is in operable communication with thepump actuator; and a bio-MEMS device in fluid communication with thedisposable cassette, the bio-MEMS device configured to collect whiteblood cells from effluent PD fluid removed from a patient, the collectedwhite blood cells used to form a patient peritonitis determination, thecontrol unit configured to communicate the peritonitis determination.

In a nineteenth aspect of the present disclosure, which may be combinedwith the eighteenth aspect in combination with any other aspect listedherein unless specified otherwise, an indication of the collected whiteblood cells is sent to the control unit, and wherein the control unit isconfigured to analyze the indication of the collected white blood cells.

In a twentieth aspect of the present disclosure, which may be combinedwith the nineteenth aspect in combination with any other aspect listedherein unless specified otherwise, the indication of the collected whiteblood cells is sent to the control unit wired or wirelessly.

In a twenty-first aspect of the present disclosure, which may becombined with the eighteenth aspect in combination with any other aspectlisted herein unless specified otherwise, the PD system includes anetwork and at least one doctor or clinician computer in communicationwith the control unit via the network, the control unit configured tocommunicate the peritonitis determination to at least one of a patientor caregiver via a user interface of the cycler or the at least onedoctor or clinician computer via the network.

In a twenty-second aspect of the present disclosure, which may becombined with the eighteenth aspect in combination with any other aspectlisted herein unless specified otherwise, the bio-MEMS device is placedin fluid communication with a sample port of the disposable cassette.

In a twenty-third aspect of the present disclosure, which may becombined with the eighteenth aspect in combination with any other aspectlisted herein unless specified otherwise, the bio-MEMS device includes acontrol unit having at least one of electronics, processing and memory,wherein either the cycler control unit or the bio-MEMS device controlunit is configured to analyze the sensed temperature.

In a twenty-fourth aspect of the present disclosure, which may becombined with the eighteenth aspect in combination with any other aspectlisted herein unless specified otherwise, the bio-MEMS device includes(i) a microfluidic chip forming a microfluidic pathway sized andconfigured to split the white blood cells from a remainder of effluentfluid and (ii) a piezoelectric biosensor that resonates with a frequencyproportional to a property of the collected white blood cells.

In a twenty-fifth aspect of the present disclosure, which may becombined with the twenty-fourth aspect in combination with any otheraspect listed herein unless specified otherwise, the property of thecollected white blood cells includes a change in the deposition rate ofthe white blood cells.

In a twenty-sixth aspect of the present disclosure, which may becombined with the twenty-fourth aspect in combination with any otheraspect listed herein unless specified otherwise, the frequencyproportional to a property of the collected white blood cells is used toform the peritonitis determination.

In a twenty-seventh aspect of the present disclosure, which may becombined with the twenty-fourth aspect in combination with any otheraspect listed herein unless specified otherwise, the piezoelectricbiosensor operates with a collection area for collecting the white bloodcells.

In a twenty-eighth aspect of the present disclosure, which may becombined with the eighteenth aspect in combination with any other aspectlisted herein unless specified otherwise, the bio-MEMS device is inwired communication with the control unit or includes a wireless modulefor wireless communication with the control unit.

In a twenty-ninth aspect of the present disclosure, which may becombined with the eighteenth aspect in combination with any other aspectlisted herein unless specified otherwise, the PD system is configured toanalyze an amount of white blood cells removed from the effluent PDfluid to make the peritonitis determination.

In a thirtieth aspect of the present disclosure, which may be combinedwith the eighteenth aspect in combination with any other aspect listedherein unless specified otherwise, the peritonitis determination is afirst peritonitis indicator, and which includes at least one differentperitonitis indicator useable in combination with the first peritonitisindicator to form an overall peritonitis determination.

In a thirty-first aspect of the present disclosure, which may becombined with the thirtieth aspect in combination with any other aspectlisted herein unless specified otherwise, the at least one differentperitonitis indicator useable in combination with the first peritonitisindicator is obtained from at least one of a patient effluent PD fluidtemperature sensor or a white blood cell impedance sensor.

In a thirty-second aspect of the present disclosure, which may becombined with the eighteenth aspect in combination with any other aspectlisted herein unless specified otherwise, the peritonitis determinationis provided in combination with insulin injection made using feedbackfrom a patient effluent glucose biosensor.

In a thirty-third aspect of the present disclosure, which may becombined with any other aspect listed herein unless specified otherwise,a peritoneal dialysis (“PD”) system includes: a cycler having a pumpactuator and a control unit in operable communication with the pumpactuator; a disposable set including a disposable cassette having a pumpchamber, the disposable cassette sized and arranged to be held by thecycler such that the pump chamber is in operable communication with thepump actuator, the disposable set including a patient line and a drainline extending from the disposable cassette; a catheter for placementwithin a patient's peritoneal cavity and for fluid communication withthe patient line; and an impedance sensor operably coupled to one of thecatheter, patient line, or drain line to sense an impedance of PD fluidresiding within the patient, or removed from the patient, the sensedimpedance used to detect white blood cells to form a patient peritonitisdetermination, the control unit configured to communicate theperitonitis determination.

In a thirty-fourth aspect of the present disclosure, which may becombined with the thirty-third aspect in combination with any otheraspect listed herein unless specified otherwise, the sensed impedance issent to the control unit, and wherein the control unit is configured toanalyze the sensed impedance.

In a thirty-fifth aspect of the present disclosure, which may becombined with the thirty-fourth aspect in combination with any otheraspect listed herein unless specified otherwise, the sensed impedance issent to the control unit wired or wirelessly.

In a thirty-sixth aspect of the present disclosure, which may becombined with the thirty-third aspect in combination with any otheraspect listed herein unless specified otherwise, the PD system includesa network and at least one doctor or clinician computer in communicationwith the control unit via the network, the control unit configured tocommunicate the peritonitis determination to at least one of a patientor caregiver via a user interface of the cycler or the at least onedoctor or clinician computer via the network.

In a thirty-seventh aspect of the present disclosure, which may becombined with the thirty-third aspect in combination with any otheraspect listed herein unless specified otherwise, the PD system includesa water purifier configured to supply purified water to the disposableset, the water purifier including a water purifier control unit, whereinthe sensed impedance is sent to the water purifier control unit, whereinthe water purifier control unit is configured to analyze the sensedimpedance, and wherein the cycler control unit and the water purifiercontrol unit are in communication to allow the cycler control unit tocommunicate the peritonitis determination.

In a thirty-eighth aspect of the present disclosure, which may becombined with the thirty-third aspect in combination with any otheraspect listed herein unless specified otherwise, the impedance sensor islocated within a connector configured to couple to the catheter, thepatient line or the drain line.

In a thirty-ninth aspect of the present disclosure, which may becombined with the thirty-eighth aspect in combination with any otheraspect listed herein unless specified otherwise, the connector is (i) aclamshell connector that fits around the catheter, the patient line orthe drain line or (ii) configured to be spliced between two sections ofthe catheter, the patient line or the drain line.

In a fortieth aspect of the present disclosure, which may be combinedwith the thirty-third aspect in combination with any other aspect listedherein unless specified otherwise, the impedance sensor includeselectrodes positioned and arranged within the catheter, the patient lineor the drain line, the connector positioned over the electrodes.

In a forty-first aspect of the present disclosure, which may be combinedwith the fortieth aspect in combination with any other aspect listedherein unless specified otherwise, the connector includes leadsextending from the electrodes to (i) the control unit, (ii) a controlunit of a water purifier configured to supply purified water to thedisposable set, or (iii) a wireless module provided with the connector.

In a forty-second aspect of the present disclosure, which may becombined with the thirty-third aspect in combination with any otheraspect listed herein unless specified otherwise, the PD system isconfigured to analyze the sensed impedance of the PD fluid residingwithin the patient, or removed from the patient, via a frequency sweepthat moves from a start frequency to a stop frequency.

In a forty-third aspect of the present disclosure, which may be combinedwith the forty-second aspect in combination with any other aspect listedherein unless specified otherwise, the frequency sweep is generated by afrequency generator provided by or operable with the control unit.

In a forty-fourth aspect of the present disclosure, which may becombined with the forty-second aspect in combination with any otheraspect listed herein unless specified otherwise, the PD system isconfigured to take an impedance measurement at two or more frequenciesof the frequency sweep.

In a forty-fifth aspect of the present disclosure, which may be combinedwith the forty-second aspect in combination with any other aspect listedherein unless specified otherwise, the frequency sweep enables fluidhaving white blood cells and residing within the patient, or removedfrom the patient, to be determined by measuring, over at least a portionof the frequency sweep, higher impedances for the fluid having whiteblood cells than impedances for fluid not having white blood cells. And,the measured impedances for fluid not having white blood cells (i) aredetermined based on standard impedances or (ii) are determined based onimpedances established for the patient.

In a forty-sixth aspect of the present disclosure, which may be combinedwith the forty-second aspect in combination with any other aspect listedherein unless specified otherwise, the frequency sweep enables fluidhaving white blood cells and residing within the patient, or removedfrom the patient, to be distinguished from fluid having fibrin, whereinthe fluid having fibrin yields higher impedances over at least a portionof the sweep than the fluid having white blood cells.

In a forty-seventh aspect of the present disclosure, which may becombined with the thirty-third aspect in combination with any otheraspect listed herein unless specified otherwise, the peritonitisdetermination is a first peritonitis indicator, and which includes atleast one different peritonitis indicator useable in combination withthe first peritonitis indicator to form an overall peritonitisdetermination.

In a forty-eighth aspect of the present disclosure, which may becombined with the forty-seventh aspect in combination with any otheraspect listed herein unless specified otherwise, the at least onedifferent peritonitis indicator useable in combination with the firstperitonitis indicator is obtained from at least one of a patienteffluent PD fluid temperature sensor or a white blood cell biosensor.

In a forty-ninth aspect of the present disclosure, which may be combinedwith the thirty-third aspect in combination with any other aspect listedherein unless specified otherwise, the peritonitis determination isprovided in combination with insulin injection made using feedback froma patient effluent glucose biosensor.

In a fiftieth aspect of the present disclosure, which may be combinedwith the thirty-third aspect in combination with any other aspect listedherein unless specified otherwise, a peritoneal dialysis (“PD”) systemincludes: a cycler including a pump actuator and a control unit inoperable communication with the pump actuator; a disposable setincluding a disposable cassette having a pump chamber, the disposablecassette sized and arranged to be held by the cycler such that the pumpchamber is in operable communication with the pump actuator; an insulinsource in fluid communication with the disposable set; and amicro-electro-mechanical-system (“MEMS”) affinity glucose sensorpositioned and arranged to receive effluent PD fluid removed from apatient, the MEMS affinity glucose sensor configured to provide aglucose assessment concerning glucose absorbed by a patient, the glucoseassessment used to determine an insulin dose, and wherein the controlunit is configured to deliver the insulin dose from the insulin sourceto the patient via the pump actuator operating with the pump chamber ofthe disposable cassette.

In a fifty-first aspect of the present disclosure, which may be combinedwith the fiftieth aspect in combination with any other aspect listedherein unless specified otherwise, the PD system includes a dialysisfluid source in fluid communication with the disposable set, and whereinthe control unit is configured to deliver the insulin dose from theinsulin source to the patient mixed with fresh dialysis fluid from thedialysis fluid source.

In a fifty-second aspect of the present disclosure, which may becombined with the fifty-first aspect in combination with any otheraspect listed herein unless specified otherwise, the dialysis fluidsource is a point of use dialysis fluid source, wherein the freshdialysis fluid is mixed within a mixing bag along with insulin from theinsulin bag.

In a fifty-third aspect of the present disclosure, which may be combinedwith the fiftieth aspect in combination with any other aspect listedherein unless specified otherwise, the disposable set includes a patientline and a drain line in fluid communication with the disposablecassette, the MEMS affinity glucose sensor in fluid communication withthe drain line.

In a fifty-fourth aspect of the present disclosure, which may becombined with the fifty-third aspect in combination with any otheraspect listed herein unless specified otherwise, the MEMS affinityglucose sensor is located along the drain line upstream of a draincontainer.

In a fifty-fifth aspect of the present disclosure, which may be combinedwith the fiftieth aspect in combination with any other aspect listedherein unless specified otherwise, the PD system includes a waterpurifier, wherein the dialysis fluid source is a point of use dialysisfluid source using purified water from the water purifier, and whereinthe MEMS affinity glucose sensor is provided with the water purifier.

In a fifty-sixth aspect of the present disclosure, which may be combinedwith the fifty-fifth aspect in combination with any other aspect listedherein unless specified otherwise, the water purifier is in wired orwireless communication with the cycler, wherein the water purifier isconfigured to determine the insulin dose from the glucose assessment anddeliver the insulin dose to the cycler for delivery.

In a fifty-seventh aspect of the present disclosure, which may becombined with the fiftieth aspect in combination with any other aspectlisted herein unless specified otherwise, the MEMS affinity glucosesensor is in wired or wireless communication with the cycler, whereinthe control unit of the cycler is configured to determine the insulindose from the glucose assessment sent from the MEMS affinity glucosesensor to the control unit.

In a fifty-eighth aspect of the present disclosure, which may becombined with the fiftieth aspect in combination with any other aspectlisted herein unless specified otherwise, the MEMS affinity glucosesensor is configured to determine the insulin dose from the glucoseassessment.

In a fifty-ninth aspect of the present disclosure, which may be combinedwith the fiftieth aspect in combination with any other aspect listedherein unless specified otherwise, the glucose assessment is indicativeof an amount or concentration of glucose absorbed by the patient.

In a sixtieth aspect of the present disclosure, which may be combinedwith the fiftieth aspect in combination with any other aspect listedherein unless specified otherwise, the MEMS affinity glucose sensorincludes (i) a microfluidic chip forming a microfluidic pathway sizedand configured to split glucose molecules from a remainder of effluentfluid and (ii) a piezoelectric biosensor that resonates with a frequencyproportional to a property of the collected glucose molecules.

In a sixty-first aspect of the present disclosure, which may be combinedwith the sixtieth aspect in combination with any other aspect listedherein unless specified otherwise, the property of the collected glucosemolecules includes a change in the deposition rate of the glucosemolecules.

In a sixty-second aspect of the present disclosure, which may becombined with the sixtieth aspect in combination with any other aspectlisted herein unless specified otherwise, the frequency proportional toa property of the collected glucose molecules is used to form theinsulin determination.

In a sixty-third aspect of the present disclosure, which may be combinedwith the sixtieth aspect in combination with any other aspect listedherein unless specified otherwise, the piezoelectric biosensor operateswith a collection area for collecting the glucose molecules.

In a sixty-fourth aspect of the present disclosure, which may becombined with the fiftieth aspect in combination with any other aspectlisted herein unless specified otherwise, the control unit is programmedassuming the lower the concentration of glucose in the effluent, thehigher the amount of glucose absorbed by the patient.

In a sixty-fifth aspect of the present disclosure, which may be combinedwith the fiftieth aspect in combination with any other aspect listedherein unless specified otherwise, the PD system includes a network andat least one doctor or clinician computer in communication with thecontrol unit via the network, the control unit configured to communicatethe insulin dose to at least one of a patient or caregiver via a userinterface of the cycler or the at least one doctor or clinician computervia the network.

In a sixty-sixth aspect of the present disclosure, which may be combinedwith the fiftieth aspect in combination with any other aspect listedherein unless specified otherwise, the PD system includes at least oneperitonitis indicating device selected from a patient effluent PD fluidtemperature sensor, a white blood cell biosensor or a white blood cellimpedance monitor.

In a sixty-seventh aspect of the present disclosure, which may becombined with any other aspect listed herein unless specified otherwise,a peritoneal dialysis (“PD”) system includes: a cycler including a pumpactuator and a control unit in operable communication with the pumpactuator; a disposable set including a pump portion sized and arrangedto be held by the cycler such that the pump portion is in operablecommunication with the pump actuator, the disposable set including apatient line and a drain line extending from the disposable cassette; acatheter for placement within a patient's peritoneal cavity and forfluid communication with the patient line; and an impedance sensoroperably coupled to one of the catheter, patient line, or drain line tosense an impedance of PD fluid residing within the patient, or removedfrom the patient, the sensed impedance used to detect white blood cellsto form a patient peritonitis determination.

In a sixty-eighth aspect of the present disclosure, which may becombined with any other aspect listed herein unless specified otherwise,a peritoneal dialysis (“PD”) system includes: a pump actuator and acontrol unit in operable communication with the pump actuator; adisposable set including a pump portion sized and arranged to be placedin operable communication with the pump actuator, the disposable setincluding a patient line and a drain line extending from the disposablecassette; a catheter for placement within a patient's peritoneal cavityand for fluid communication with the patient line; and an impedancesensor operably coupled to one of the catheter, patient line, or drainline to sense PD fluid residing within the patient, or removed from thepatient, over a frequency sweep that moves from a start frequency to astop frequency, the sensed impedance frequency sweep used to detectwhite blood cells to form a patient peritonitis determination.

In a sixty-ninth aspect of the present disclosure, any of the structureand functionality disclosed in connection with FIGS. 1 to 20B may beincluded or combined with any of the other structure and functionalitydisclosed in connection with FIGS. 1 to 20B.

In light of the present disclosure and the above aspects, it istherefore an advantage of the present disclosure to provide an improvedperitoneal dialysis (“PD”) system and method.

It is another advantage of the present disclosure to provide a PD systemand method that enable peritonitis to be determined on an objectivebasis.

It is a further advantage of the present disclosure to provide a PDsystem and method that enable peritonitis to be determined automaticallywithout over-burdening the patient.

It is still another advantage of the present disclosure to provide a PDsystem and method that enable peritonitis to be determined usingmultiple different procedures that provide cross-checking.

It is still a further advantage of the present disclosure to provide aPD system and method that proportion insulin infusion with dialysisfluid infusion at a desired concentration.

It is yet another advantage of the present disclosure to provide a PDsystem and method that communicate relevant peritonitis and insulininfusion data remotely to a clinician.

The advantages discussed herein may be found in one, or some, andperhaps not all of the embodiments disclosed herein. Additional featuresand advantages are described herein, and will be apparent from, thefollowing Detailed Description and the figures.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 is a front elevation view of one embodiment of a peritonealdialysis delivery system having point of use dialysis fluid production,which communicates with a remote doctor or clinician data collectionregime.

FIG. 2 is a top plan view of one embodiment of a disposable set usedwith the system illustrated in FIG. 1.

FIG. 3 is a front elevation view of one embodiment of a temperaturesensing connector of the present disclosure.

FIGS. 4A and 4B are front elevation and perspective views, respectively,of another embodiment of a temperature sensing connector of the presentdisclosure.

FIG. 5 is a side elevation view of a further embodiment of a temperaturesensing connector of the present disclosure.

FIG. 6 is a schematic view of one embodiment of a wirelessly operatedtemperature sensing connector of the present disclosure.

FIGS. 7A and 7B are schematic plots showing outputs of varioustemperature sensing connectors of the present disclosure.

FIGS. 8A and 8B are schematic plots showing outputs of other temperaturesensing connectors of the present disclosure.

FIG. 9 is a front elevation view of a medical fluid delivery systemhaving point of use dialysis fluid production, which operates with oneembodiment of a white blood cell sensing device of the presentdisclosure.

FIG. 10 is a schematic flow diagram of one embodiment of a white bloodcell sensing method useable with the system of FIG. 9.

FIG. 11 is a front elevation view of a medical fluid delivery systemhaving point of use dialysis fluid production, which operates with oneembodiment of an effluent fluid impedance evaluation device of thepresent disclosure.

FIG. 12 is a front isometric view of one embodiment for electrodeplacement within a catheter or tube operating with an effluent fluidimpedance evaluation device of the present disclosure.

FIG. 13 is a front elevation view of one embodiment for a catheterimpedance effluent evaluation device of the present disclosure.

FIGS. 14A and 14B are schematic plots showing impedance outputs overtime and over a frequency sweep, respectively, for normal patienteffluent, patient effluent having white blood cells (indicatingperitonitis) and patient effluent having fibrin.

FIG. 15 is a front elevation view of a medical fluid delivery systemoperating with presterilized containers of peritoneal dialysis fluid,which further operates with one embodiment of an effluent glucosesensing and insulin controlling device of the present disclosure.

FIG. 16 is a front elevation view of one embodiment of a MEMS affinityglucose sensor useable with the systems of FIGS. 15 and 17.

FIG. 17 is a front elevation view of a medical fluid delivery systemhaving point of use dialysis fluid production, which operates with oneembodiment for an effluent glucose sensing and insulin controllingdevice of the present disclosure.

FIG. 18 is a schematic flow diagram of one embodiment of an effluentglucose sensing and insulin controlling method useable with the systemsof FIGS. 15 and 16.

FIG. 19 is a schematic plot showing a relationship between frequencyoutput of a MEMS affinity glucose sensor and effluent glucose level.

FIGS. 20A and 20B are schematic plots showing patient glucose level whenuncontrolled during peritoneal dialysis treatment and controlled via theglucose feedback and insuling injection of FIGS. 15 to 18.

DETAILED DESCRIPTION System Overview

The feedback systems and methods described herein are applicable withperitoneal dialysis (“PD”). The feedback systems and methods are mainlyapplicable to automated peritoneal dialysis (“APD”), which involves theuse of a PD machine or cycler. It should be appreciated however thatfeedback systems and methods are also applicable to continuousambulatory peritoneal dialysis (“CAPD”). With CAPD, the feedback systemsand methods are implemented in stand alone devices that read out to thepatient and/or communicate data remotely to a caregiver database forreview by a doctor or clinician. Regarding APD machines, suitablecyclers include, e.g., the Amia® or HomeChoice® cycler marketed byBaxter International Inc. For example, the Amia® cycler is disclosed inU.S. Pat. No. 9,981,079, while the HomeChoice® cycler is disclosed inU.S. Pat. No. 5,350,357, the contents of each of which are incorporatedby reference and relied upon. The above-incorporated patents eachdisclose the use of pre-packaged, pre-sterilized container or bags of PDdialysis fluid. The feedback systems and methods are applicable andimplementable with cyclers using pre-packaged, pre-sterilized PD fluid.As discussed below, the feedback systems and methods are also applicableand implementable with cyclers using PD fluid made online or at thepoint of use.

Referring now to FIG. 1, one embodiment of a peritoneal dialysis systemhaving point of use dialysis fluid production is illustrated by system10. System 10 includes a cycler 20 and a water purifier 210. Suitablecyclers for cycler 20 include, e.g., the Amia® or HomeChoice® cycler asmentioned above, with the understanding that those cyclers are providedwith updated programming to perform and use the point of use dialysisfluid produced according to system 10. To this end, cycler 20 includes acontrol unit 22 having at least one processor and at least one memory.Control unit 22 further includes a wired or wireless transceiver forsending information to and receiving information from a water purifier210 and other wireless devices discussed herein. Water purifier 210 alsoincludes a control unit 212 having at least one processor and at leastone memory. Control unit 212 further includes a wired or wirelesstransceiver for sending information to and receiving information fromcontrol unit 22 of cycler 20 and other wireless devices discussedherein. Wired communication may be via Ethernet connection, for example.Wireless communication may be performed via any of Bluetooth™, WiFi™,Zigbee®, Z-Wave®, wireless Universal Serial Bus (“USB”), or infraredprotocols, or via any other suitable wireless communication technology.

Cycler 20 includes a housing 24, which holds equipment programmed viacontrol unit 22 to prepare fresh dialysis solution at the point of use,pump the freshly prepared dialysis fluid to patient P, allow thedialysis fluid to dwell within patient P, then pump used dialysis fluidto a drain. In the illustrated embodiment, water purifier 210 includes adrain line 214 leading to a drain 216, which can be a house drain or adrain container. The equipment programmed via control unit 22 to preparefresh dialysis solution at the point of use in an embodiment includesequipment for a pneumatic pumping system, including but not limited to(i) one or more positive pressure reservoir, (ii) one or more negativepressure reservoir, (iii) a compressor and a vacuum pump each undercontrol of control unit 22, or a single pump creating both positive andnegative pressure under control of control unit 22, to provide positiveand negative pressure to be stored at the one or more positive andnegative pressure reservoirs, (iv) plural pneumatic valve chambers fordelivering positive and negative pressure to plural fluid valvechambers, (v) plural pneumatic pump chambers for delivering positive andnegative pressure to plural fluid pump chambers, (vi) pluralelectrically actuated on/off pneumatic solenoid valves under control ofcontrol unit 22 located between the plural pneumatic valve chambers andthe plural fluid valve chambers, (vii) plural electrically actuatedvariable orifice pneumatic valves under control of control unit 22located between the plural pneumatic pump chambers and the plural fluidpump chambers, (viii) a heater under control of control unit 22 forheating the dialysis fluid as it is being mixed in one embodiment, and(ix) an occluder 26 under control of control unit 22 for closing thepatient and drain lines in alarm and other situations.

In one embodiment, the plural pneumatic valve chambers and the pluralpneumatic pump chambers are located on a front face or surface ofhousing 24 of cycler 20. The heater is located inside housing 24 and inan embodiment includes heating coils that contact a heating pan or tray,which is located at the top of housing 24, beneath a heating lid (notseen in FIG. 1).

Cycler 20 in the illustrated embodiment includes a user interface 30.Control unit 22 in an embodiment includes a video controller, which mayhave its own processing and memory for interacting with primary controlprocessing and memory of control unit 22. User interface 30 includes avideo monitor 32, which may operate with a touch screen overlay placedonto video monitor 32 for inputting commands via user interface 30 intocontrol unit 22. User interface 30 may also include one or moreelectromechanical input device, such as a membrane switch or otherbutton. Control unit 22 may further include an audio controller forplaying sound files, such as voice activation commands, at one or morespeaker 34.

Water purifier 210 in the illustrated embodiment also includes a userinterface 220. Control unit 212 of water purifier 210 in an embodimentincludes a video controller, which may have its own processing andmemory for interacting with primary control processing and memory ofcontrol unit 212. User interface 220 includes a video monitor 222, whichmay likewise operate with a touch screen overlay placed onto videomonitor 222 for inputting commands into control unit 212. User interface220 may also include one or more electromechanical input device, such asa membrane switch or other button. Control unit 212 may further includean audio controller for playing sound files, such as alarm or alertsounds, at one or more speaker 224 of water purifier 210.

Referring additionally to FIG. 2, one embodiment of disposable set 40 isillustrated. Disposable set 40 is also illustrated in FIG. 1, mated tocycler 20 to move fluid within the disposable set 40, e.g., to mixdialysis fluid as discussed herein. Disposable set 40 in the illustratedembodiment includes a disposable cassette 42, which may include a planarrigid plastic piece covered on one or both sides by a flexible membrane.The membrane pressed against housing 24 of cycler 20 forms a pumping andvalving membrane. FIG. 2 illustrates that disposable cassette 42includes fluid pump chambers 44 that operate with the pneumatic pumpchambers located at housing 24 of cycler 20 and fluid valve chambers 46that operate with the pneumatic valve chambers located at housing 24 ofcycler 20.

FIGS. 1 and 2 illustrate that disposable set 40 includes a patient line50 that extends from a patient line port of cassette 42 and terminatesat a patient line connector 52. FIG. 1 illustrates that patient lineconnector 52 connects to a patient transfer set 54, which in turnconnects to an indwelling catheter located in the peritoneal cavity ofpatient P (see FIG. 11). Disposable set 40 includes a drain line 56 thatextends from a drain line port of cassette 42 and terminates at a drainline connector 58. FIG. 1 illustrates that drain line connector 58connects removeably to a drain connector 218 of water purifier 210.

FIGS. 1 and 2 further illustrate that disposable set 40 includes aheater/mixing line 60 that extends from a heater/mixing line port ofcassette 42 and terminates at a heater/mixing bag 62 discussed in moredetail below. Disposable set 40 includes an upstream water line segment64 a that extends to a water inlet 66 a of water accumulator 66. Adownstream water line segment 64 b extends from a water outlet 66 b ofwater accumulator 66 to cassette 42. In the illustrated embodiment,upstream water line segment 64 a begins at a water line connector 68 andis located upstream from water accumulator 66. FIG. 1 illustrates thatwater line connector 68 is removeably connected to a water outletconnector 228 of water purifier 210.

Water purifier 210 outputs water and possibly water suitable forperitoneal dialysis (“WFPD”). To ensure WFPD, however, a sterilizinggrade filter 70 a is placed upstream from a downstream sterilizing gradefilter 70 b, respectively. Filters 70 a and 70 b may be placed in waterline segment 64 a upstream of water accumulator 66. Sterilizing gradefilters 70 a and 70 b may be pass-through filters that do not have areject line. Suitable sterilizing grade filters 70 a and 70 b may beprovided by the assignee of the present disclosure. In an embodiment,only one of upstream or downstream sterilizing grade filter 70 a and 70b is needed to produce WFPD, nevertheless, two sterilizing grade filters70 a and 70 b are provided in the illustrated embodiment for redundancyin case one fails.

FIG. 2 further illustrates that a last bag or sample line 72 may beprovided that extends from a last bag or sample port of cassette 42.Last bag or sample line 72 terminates at a connector 74, which may beconnected to a mating connector of a premixed last fill bag of dialysisfluid or to a sample bag or other sample collecting container. Last bagor sample line 72 and connector 74 may be used alternatively for a thirdtype of concentrate if desired.

FIGS. 1 and 2 illustrate that disposable set 40 includes a first, e.g.,glucose, concentrate line 76 extending from a first concentrate port ofcassette 42 and terminates at a first, e.g., glucose, cassetteconcentrate connector 80 a. A second, e.g., buffer, concentrate line 78extends from a second concentrate port of cassette 42 and terminates ata second, e.g., buffer, cassette concentrate connector 82 a.

FIG. 1 illustrates that a first concentrate container 84 a holds afirst, e.g., glucose, concentrate, which is pumped from container 84 athrough a container line 86 to a first container concentrate connector80 b, which mates with first cassette concentrate connector 80 a. Asecond concentrate container 84 b holds a second, e.g., buffer,concentrate, which is pumped from container 84 b through a containerline 88 to a second container concentrate connector 82 b, which mateswith second cassette concentrate connector 82 a.

In an embodiment, to begin treatment, patient P loads cassette 42 intocycler and in a random or designated order (i) places heater/mixing bag62 onto cycler 20, (ii) connects upstream water line segment 64 a towater outlet connector 228 of water purifier 210, (iii) connects drainline 56 to drain connector 218 of water purifier 210, (iv) connectsfirst cassette concentrate connector 80 a to first container concentrateconnector 80 b, and (v) connects second cassette concentrate connector82 a to second container concentrate connector 82 b. At this point,patient connector 52 is still capped. Once fresh dialysis fluid isprepared and verified, patient line 50 is primed with fresh dialysisfluid, after which patient P may connect patient line connector 52 totransfer set 54 for treatment. Each of the above steps may beillustrated graphically at video monitor 32 and/or be provided via voiceguidance from speakers 34.

For disposable set 40, the rigid portion of cassette 42 may be made forexample of a medically acceptable rigid plastic. The flexible membranesof cassette 42 may be made for example of medically acceptable rigidplastic sheeting. Any of the bags or containers, such as heater/mixingbag or container 62 discussed below, may be made of medically acceptableplastic sheeting.

Control unit 22 may be programmed to cause cycler 20 to perform one ormore mixing action to help mix dialysis fluid properly and homogeneouslyfor treatment. For example, any of fluid pump chambers 44 may be causedto withdraw into the pump chambers some amount of mixed fluid (e.g.,made from one or both first and second concentrates 84 a, 84 b and WFPD)from heater/mixing bag 62 and send such mixture back to heater/mixingbag 62 and repeat this procedure multiple times (described herein as amixing sequence or “waffling”). In particular, to perform a mixingsequence, control unit 22 in an embodiment causes cycler 20 to close allfluid valve chambers 46 at cassette 42 except for the fluid valvechamber 46 to heater/mixing line 60 and heater/mixing bag 62. Fluid pumpchambers 44 are stroked sequentially and repeatedly (i) pulling apossibly unmixed fluid combination of WFPD and concentrates fromheater/mixing bag 62 into the pump chambers, followed by (ii) pushingthe mixed WFPD and concentrates from the pump chambers back toheater/mixing bag 62 and (iii) repeating (i) and (ii) at least one time.Control unit 22 may be programmed to stroke fluid pump chambers 44together so that they both pull and push at the same time, oralternatingly so that one pump chamber 44 pulls from heater/mixing bag62, while the other pump chamber 44 pushes to heater/mixing bag 62,creating turbulence in heater/mixing line 60.

The configuration of container or bag 62 operable with cassette 42 andheater/mixing line 60 as illustrated in FIGS. 1 and 2 enables the WFPDfrom accumulator 66 and concentrates from first and second concentratecontainers 84 a and 84 b to at least partially mix before entering thecontainer or bag. Also, even if cassette 42 is not provided, the WFPDand at least one concentrate will mix partially in heater/mixing line 60prior to reaching the container or bag.

FIG. 1 also illustrates that system 10 in one embodiment communicatesvia a network 100 with one or more caregiver server 102, which in turnis placed in operable communication with one or more doctor or cliniciancomputer 110 to 110 c. In the illustrated embodiment, network 100 is acloud network, e.g., using one or more wide area network (“WAN”), suchas an internet. Network 100 may alternatively be a more local areanetwork (“LAN”). In the illustrated embodiment, cycler 20 of system 10communicates with network 100 wirelessly via any of the protocols listedherein. In an alternative embodiment, cycler 20 of system 10communicates with network 100 in a wired manner, e.g., using an Ethernetconnection. In the illustrated embodiment, cycler 20 of system 10communicates with network 100. In an alternative embodiment, waterpurifier 210 communicates alternatively or additionally with network 100in a wireless or wired manner. In the illustrated embodiment, one ormore caregiver server 102 communicates with network 100 wirelessly viaany of the protocols listed herein. In an alternative embodiment, one ormore caregiver server 102 communicates with network 100 in a wiredmanner, e.g., using an Ethernet connection. In the illustratedembodiment, doctor or clinician computers 110 to 110 c communicate withone or more caregiver server 102 in a wired manner, e.g., using Ethernetconnections. In an alternative embodiment, doctor or clinician computers110 to 110 c communicate with one or more caregiver server 102wirelessly via any of the protocols listed herein.

Temperature Sensing for Peritonitis

Referring now to FIGS. 3 to 8B, in one primary embodiment, thetemperature of used dialysis fluid exiting the patient is measured todetect peritonitis. In healthy patients, the temperature of useddialysis fluid is normal body temperature or about 37° C. In patientsexperiencing the onset of peritonitis, the used dialysis fluid exitingthe patient may reside at an elevated temperature. The system and methodof the first embodiment measure the effluent dialysis fluid and use themeasurement to make a determination as to whether the patient may beexperiencing the onset of peritonitis.

The temperature measurement may be made in a number of different ways.Temperature sensing connector 120 in FIG. 3 illustrates one mechanismfor reading the temperature of the effluent fluid removed from patient P(FIG. 1). Connector 120 includes a primary housing 122, which may bemade of any suitable medical grade material, such as a medical gradeplastic. In the illustrated embodiment, housing 122 is spliced intopatient line 50 (FIG. 1). Housing 122 includes a first port 124 thatsealingly accepts a first spliced end 50 a of patient line 50. Firstport 124 may for example include or be a hose barb port or be sized tostretch first spliced end 50 a as illustrated. First port 124 mayalternatively be a luer connector connecting to a mating luer connectorend 50 a of patient line 50. Housing 122 includes a second port 126 thatsealingly accepts a second spliced end 50 b of patient line 50. Secondport 126 may be a male port just like port 124 or be a female port asillustrated which sealingly accepts second spliced end 50 b via acompression fitting (to do so second spliced end 50 b may be fitted withan internal rigid hose barb to maintain their shape of spliced end 50 bwhen placed under compression). Female port 126 enables electrical leads128 a and 128 b to extend out of housing 122 in the event thatelectrical signals are delivered via wire to control unit 22 of cycler10 (or control unit 212 of water purifier 210).

Electrical leads 128 a and 128 b extend to probes or electrodes 130 aand 130 b, respectively, which contact effluent fluid traveling throughhousing 122 and provide a temperature reading for the fluid. Leads 128 aand 128 b and electrodes 130 a and 130 b may be overmolded into oradhered to the inner cylindrical surface of housing 122. The temperaturesensor of connector 120 may be for example a thermocouple or thermistor.In the illustrated embodiment, electrodes 130 a and 130 b are thesensing portion of a K-type (chromel-alumel) thermocouple, whichgenerates a voltage that may be sensed and which is proportional to atemperature of the effluent fluid.

Connector 120 illustrates multiple ways in which the generated voltagemay be analyzed (as alternatives so not all of the structure illustratedin FIG. 3 needs be provided with connector 120, just the structureused). In one embodiment, leads 128 a and 128 b carry the generatedvoltage back to control unit 22 of cycler 20 (or control unit 212 ofwater purifier 210), wherein the electronics and processing of thecontrol unit process the temperature proportional voltage signal anddetermine if the resulting temperature indicates peritonitis or theonset thereof.

In another embodiment (indicated by dashed lines), leads 128 a and 128 bcarry the generated voltage to a wireless module 132 located along theoutside of housing 122. Wireless module 132 is powered by a battery 134,such as a long-lasting lithium battery, and includes electronicsconfigured to convert the temperature proportional voltage to a wirelesssignal, which is sent wirelessly to control unit 22 of cycler 20 in oneembodiment. Control unit 22 of cycler 20 processes the wireless versionof the temperature proportional voltage signal and determines if theresulting temperature indicates peritonitis or the onset thereof.

FIG. 3 illustrates an embodiment in which the connector is spliced inbetween two tubing segments. FIGS. 4A and 4B illustrate an alternativeembodiment in which a clamshell temperature connector 140 instead fitsover a tubing segment, such as a portion of patient line 50. In theillustrated embodiment, clamshell temperature connector 140 firstdirectly over and contacts the medical grade polymer or plastic ofpatient line 50. In an alternative embodiment, a more thermallyconductive medical grade segment 150, such as a stainless steel segment,is spliced in between two polymer or plastic segments of patient line50. The more thermally conductive medical grade segment 150 may help toachieve a more accurate temperature measurement.

FIGS. 4A and 4B illustrate that clamshell temperature connector 140includes a housing 142 having clamshell halves 144 and 146, which arehinged together along a living hinge 148 in the illustrated embodiment.Housing 142 is made of any suitable material, such as a medical gradeplastic. Housing 142 is sized to form fit over patient line 50/150 inthe illustrated embodiment.

Connector 140 includes electrical leads 152 a and 152 b that extend toprobes or electrodes 154 a and 154 b, respectively, which contactpatient line 50/150 to provide a temperature of the effluent fluidflowing through the line. Leads 152 a and 152 b and electrodes 154 a and154 b may be overmolded into or adhered to the inner cylindrical surfaceof respective clamshell halves 144 and 146. The temperature sensor ofconnector 140 may again be a thermocouple or thermistor. In theillustrated embodiment, electrodes 154 a and 154 b are the sensingportion of a K-type (chromel-alumel) thermocouple, which generates avoltage that may be sensed and which is indicative of a temperature ofthe effluent fluid.

Connector 140 illustrates multiple ways in which the generated voltagemay be analyzed (as alternatives so not all structure illustrated inFIGS. 4A and 4B needs to be provided with connector 140, just thestructure used). In one embodiment, leads 152 a and 152 b carry thegenerated voltage back to control unit 22 of cycler 20 (or control unit212 of water purifier 210), wherein the electronics and processing ofthe control unit processes the temperature proportional voltage signaland determines if the resulting temperature indicates peritonitis or theonset thereof.

In another embodiment (indicated by dashed lines), leads 152 a and 152 bcarry the generated voltage to wireless module 132 located along theoutside of housing 142. Wireless module 132 is powered by a battery 134,such as a long-lasting lithium battery, and includes electronicsconfigured to convert the temperature proportional voltage to a wirelesssignal, which is sent wirelessly to control unit 22 of cycler 20 in oneembodiment. Control unit 22 of cycler 20 processes the wireless versionof the temperature proportional voltage signal and determines if theresulting temperature indicates peritonitis or the onset thereof.

FIG. 5 illustrates a further alternative embodiment in which a snap-fittemperature connector 160 is fitted to a wall of housing 24 of cycler 20(or a wall of water purifier 210), either inside of outside of themachine. Snap-fit temperature connector 160 includes a housing 162,which is bolted to, adhered to, or formed by housing 24. Housing 162 ismade of any suitable material, such as a medical grade plastic. Housing162 includes a snap-fitting collar 164, which in combination with probesor electrodes 166 a and 166 b are sized to snap-fit over patient line50/150 in the illustrated embodiment. The C-shaped collar 164 spreadsapart slightly to accept patient line 50/150 and then spreads apartslightly again to release patient line 50/150 once treatment iscompleted.

Electrodes 166 a and 166 b may be overmolded into or adhered to theinner cylindrical surface of C-shaped collar 164. The temperature sensorof connector 160 may again be a thermocouple or thermistor. In theillustrated embodiment, electrodes 166 a and 166 b are the sensingportion of a K-type (chromel-alumel) thermocouple, which generates avoltage that may be sensed and which is indicative of a temperature ofthe effluent fluid. In the illustrated embodiment, electrodes 166 a and166 b extend respectively to leads 168 a and 168 b, which carry thegenerated voltage through the wall of housing 24 and to control unit 22of cycler 20 (or control unit 212 of water purifier 210), wherein theelectronics and processing of the control unit processes the temperatureproportional voltage signal and determines if the resulting temperatureindicates peritonitis or the onset thereof.

FIG. 6 illustrates schematically the wireless version of the temperaturesensing of the first primary embodiment. Patient line 50 or thermallyconductive patient line segment 150 carries effluent fluid. Electrodes E(representing all electrodes discussed above) contact the outer wall ofpatient line 50 or thermally conductive patient line segment 150 asillustrated or contact the effluent fluid directly (FIG. 3). Atemperature indicating voltage is carried via leads L (representing allleads discussed above) to wireless module 132. Wireless module 132 ispowered by a battery 134, such as a long-lasting lithium battery, andincludes electronics configured to convert the temperature proportionalvoltage to a wireless signal, which is sent wirelessly to a desiredcontrol unit.

FIG. 6 also illustrates another alternative embodiment in whichelectrodes E are located instead along the sheeting of disposablecassette disposable cassette 42. Here, the electrodes E are locatedinside cycler 20 and are aligned automatically with cassette 42 when thecassette is installed. The patient or caregiver is not required to takeany additional action. In this scenario, wireless module 132 is notneeded and leads L run instead directly to control unit 22.

As discussed above, testing the temperature of the effluent fluid ofpatient P is used to determine if the patient has peritonitis. Theeffluent fluid flows from patient P, though patient transfer set 54,patient line connector 52, patient line 50, disposable set 40, drainline 56, drain line connector 58, and drain connector 218 of waterpurifier 210. It is contemplated to place temperature sensing connectors120, 140 or 160 at any of those locations, including as part of patienttransfer set 54, patient line connector 52 or drain line connector 58.In one aspect, it is advantageous to place temperature sensingconnectors 120, 140 or 160 as close to patient P as possible, e.g., atpatient transfer set 54 or patient line connector 52, so as to sense asaccurate a patient effluent temperature as possible. As shown belowhowever, temperature sensing may be useful for the present purpose evenif the true patient temperature is not sensed. Locating the temperaturesensing for peritonitis along the drain line within water purifier 210is advantageous if for example a temperature sensor already exists therefor another purpose, such as to work in combination with a conductivitysensor to test the conductivity of dialysis fluid to determine mixingaccuracy.

FIGS. 7A and 7B illustrate example data from either a direct fluidsensing embodiment (e.g., connector 120 of FIG. 3) or sensing through athermally conductive patient tube segment 150 embodiment, each of whichshould read true fluid temperature. FIGS. 7A and 7B each showtemperature reading for two fill phases (Fi1 and Fi2) and two drainphases (Dr1 and Dr2). Each fill phase is followed by a dwell periodindicated by parallel lines. Each drain phase is followed by the nextfill phase as indicated by a single vertical line.

Cycler 20 heats fresh dialysis fluid in heater/mixing bag 62 to bodytemperature or 37° C. prior to delivery via cassette 42 and patient line50 to patient P. In each fill phase instance in FIGS. 7A and 7B, thetemperature reading is at or about 37° C. as heated fresh fluid flowspast the temperature sensor. The drain phase readings (Dr1 and Dr2) arethe readings of effluent dialysis fluid from patient P, wherein theeffluent fluid has resided within the patient for a prolonged period oftime, e.g., at least one hour, such that the effluent fluid temperatureprovides a true indication of the patient's internal body temperature.FIG. 7A shows effluent temperature readings from a healthy PD patient,in which the readings may be at or slightly above body temperature or37° C. FIG. 7B shows effluent temperature readings from a PD patient whomay be experiencing peritonitis or the onset thereof, in which thereadings are noticeably above body temperature, around 38° C. in theillustrated example.

It is contemplated to program temperature signal manipulation inevaluating the temperature readings. For example, assume the setpointfor generating a peritonitis alert is 38° C. The relevant processing andmemory evaluating the temperature readings may be programmed to averagethe temperature readings over the course of the drain flow of effluentfluid past the temperature sensor. In this manner, a short temperaturespike to 38° C. does not trigger an alert or flag. It is alsocontemplated to look to temperature readings over multiple effluentdrains (e.g., Dr1 and Dr2), and to average same prior to making adetermination whether or not to generate a peritonitis alert. Forexample, an alert is generated in one embodiment at the end of atreatment including multiple effluent drains when the totality ofeffluent temperature readings indicates peritonitis or the onsetthereof, e.g., 38° C. or higher.

FIGS. 8A and 8B illustrate example data from a sensing through agenerally non-thermally conductive patient tube segment 50 embodiment,wherein the temperature read may be below the true fluid temperature.FIGS. 8A and 8B each show temperature readings for two fill phases (Fi1and Fi2) and two drain phases (Dr1 and Dr2). Each fill phase is followedby a dwell period indicated by parallel lines. Each drain phase isfollowed by the next fill phase as indicated by a single vertical line.

Because it is known that cycler 20 heats fresh dialysis fluid inheater/mixing bag 62 to body temperature or 37° C. prior to delivery viacassette 42 and patient line 50 to patient P, the temperatures of thefill phases in FIGS. 8A and 8B provide an accurate indication of thetemperature reading offset due to the generally non-thermally conductivenature of the tubing of patient line 50 (e.g., polyvinyl-chloride(“PVC”)). In the illustrated example of FIGS. 8A and 8B, the temperatureof the the heated fresh PD fluid reads 32° C. instead of what is knownto be 37° C. The relevant control unit 22 or 212 thereby determines thatthe present offset for the present tubing under the presentenvironmental conditions is 5° C. The relevant control unit isprogrammed to then expect the effluent fluid removed from a healthypatient P to have roughly the same temperature offset, namely, to bearound 32° C. The relevant control unit is also programmed to determinethat patient P may have peritonitis if the temperature of the effluentfluid removed from the patient is a predefined amount above theoffsetted temperature of around 32° C.

In each fill phase instance in FIGS. 8A and 8B, the offsettedtemperature reading through the generally thermally non-conductivepatient line tubing 50 is at or about 32° C. as heated fresh fluid flowspast the temperature sensor. The drain phase readings (Dr1 and Dr2) areagain the readings of effluent dialysis fluid from patient P, whereinthe effluent fluid has resided within the patient for a prolonged periodof time, e.g., at least one hour, such that the effluent fluidtemperature provides a true indication of the patient's internal bodytemperature. FIG. 8A shows effluent temperature readings from a healthyPD patient, in which the readings may be at or slightly above theexpected offsetted temperature of 32° C. FIG. 8B however shows effluenttemperature readings from a PD patient who may be experiencingperitonitis or the onset thereof, in which the readings are noticeablyabove the expected offsetted temperature, around 34° C. in theillustrated example. For the expected offset example of FIGS. 8A and 8B,it is again contemplated to program the above-described temperaturesignal manipulation, e.g., averaging and accumulating over multiplefills and drains, in evaluating the temperature readings.

In the examples of FIGS. 7A to 8B, when the relevant control unit 22 or212 determines that patient P may be experiencing peritonitis or theonset thereof, the control unit in one embodiment causes user interface30 and/or 220 to provide an audio, visual or audiovisual alert to thepatient and/or caregiver at cycler 20 and/or water purifier 210 ofsystem 10. In one embodiment, even if the control unit evaluating thetemperature readings for the peritonitis determination is control unit212 of water purifier 210, the audio, visual or audiovisual alert isnevertheless provided at user interface 30 of cycler 20 by way of awired or wireless communication from control unit 212 of water purifier210 to control unit 22 of cycler 20 informing of the alert condition. Inthis manner, user interface 30 is the primary communication vehicle fora given treatment and patient P, and wherein user interface 220 isrelegated to displaying water purifier related information.

In addition or perhaps alternatively to the alert provided to patient Por caregiver at user interface 30 of cycler 20, control unit 22 (orperhaps control unit 212) operates via network 100 and one or morecaregiver server computer 102 to enable a doctor or clinician at one ormore clinician computer 110 a to 110 c to receive and view effluenttemperature data, e.g., on an ongoing basis, so that the doctor orclinician may determine if the patient has or is at risk of developingperitonitis. The data is displayed on clinician computer 110 a to 110 cin one embodiment via a dashboard of a website for the patient, whereinthe temperature data may be presented with a flag for the clinician whenit is elevated, indicating peritonitis.

It is contemplated to send effluent temperature data for patient P afterevery treatment regardless of whether the data indicates peritonitis. Inthis way, the doctor or clinician is able to develop a pattern orprofile of effluent temperatures for the patient. It is contemplatedthat the website develops a graph or trend of effluent temperatures thatare plotted against treatment dates, which is displayed upon request,for example, in addition to the dashboard. The trend as well as thedashboard in one embodiment pinpoints or flags temperature entries thatmay indicate peritonitis or the onset thereof. A doctor or clinicianviewing multiple flagged peritonitis days is therefore able to determinewith reasonable certainty that the patient needs treatment.

Bio-MEMS Sensing for Peritonitis

Referring now to FIGS. 9 and 10, in a second primary embodiment, abio-Micro-Electro-Mechanical-System (“bio-MEMS”) sensor is used todetect peritonitis. The bio-MEMS sensor is used to look for the presenceof white blood cells from the patient in the effluent fluid, which is anindicator of peritonitis. FIG. 9 illustrates that in one implementation,effluent fluid from patient P is pumped via patient line 50 to cassette42 loaded into cycler 20 and pumped thereafter from cassette 42 viadrain line 56 to a drain at water purifier 210. Drain line 56 isconnected to a lab-on-chip diagnostic detection or bio-MEMS device 170in one embodiment. In the illustrated embodiment of FIG. 9 however analternative is shown in which effluent fluid is pumped selectively viaan extra sample port 48 and a sample line 158 to lab-on-chip diagnosticdetection device 170. Using sample port 48 enables control unit 22 ofcycler 20 to selectably deliver a desired amount of effluent fluid frompatient P to lab-on-chip diagnostic detection device 170 at a desiredtime and/or frequency.

As illustrated in FIG. 9, lab-on-chip or bio-MEMS device 170 includes acontainer 172 to which a sampling line 158 extends and connects (e.g.,via compression fitting, threaded fitting, luer connection, hose barbconnection and combinations thereof) to an inlet line 174 located withincontainer 172. Container 172 may be made of a medically acceptable metalor polymer, such as stainless steel or plastic such as PVC.

The effluent sample travels along inlet line 174 of bio-MEMS device 170to a microfluidic pathway 178 formed on or in a microfluidic chip 176.Microfluidic chip 176 in various embodiments is made from inorganicmaterials, polymeric materials or paper. In various embodiments,microfluidic chip 176 is made of silicon, glass, polymer substrates,composites or paper. Microfluidic pathway 178 is sized and configured tosplit the patient's white blood cells from the remainder of effluentfluid.

The split off white blood cells are then delivered to a collection area180 (made of the same material as container 172 or microfluidic chip 176in various embodiments) where they are weighed or otherwise quantifiedby a piezoelectric biosensor 182. Piezoelectric sensor 182 in variousembodiments uses a piezoelectric effect to measure a change in pressure,strain, or force due to the collected white blood cells by convertingthe changes to an electrical charge. In an embodiment, piezoelectricbiosensor 182 resonates with a frequency proportional to a change in thedeposition rate of white blood cells.

In the illustrated embodiment, bio-MEMS device 170 includes a controlunit 184 having electronics, processing and memory to convert thefrequency of resonation from biosensor 182 into a quantified amountrepresenting the amount of white blood cells removed from the patient'seffluent sample. Control unit 184 may also include a user interface 186that displays an audio, visual or audiovisual message to the patient orcaregiver indicating the presence or not of white blood cells and thusthe presence or not of peritonitis or the onset thereof.

Alternatively, bio-MEMS device 170 includes electronics configured toconvert the white blood cell quantity proportional voltage to a wirelesssignal as illustrated in FIG. 9, which is sent wirelessly to controlunit 22 of cycler 20 in one embodiment. Here, user interface 186 is notneeded and user interface 30 of cycler 20 is used instead. Processingand memory for device 170 may also not be needed.

Method 190 of FIG. 10 summarizes the methodology just described. At oval192, method 190 begins. At block 194, patient P's effluent discharge iscollected, e.g., via separate sample port 48 of cassette 42 and sampleline 158 discussed above. At block 196, white blood cells if present areseparated from the patient's effluent fluid, e.g., via microfluidic chip176. At block 198, the separated white blood cells are weighed orotherwise quantified, e.g., via piezoelectric biosensor 182. At block200, the white blood cell weight is converted into an electrical signal,e.g., via piezoelectric biosensor 182. At block 202, the electricalsignal is processed into a form that may be used by control unit 22 (ofcycler 20) or control unit 184 (of bio-MEMS device 170) to determine ifthe amount of white blood cells collected indicates peritonitis or theonset thereof. There may be an amount of white blood cells below whichperitonitis is not presumed to be present. At block 204, the results ofthe white blood cell analysis are displayed at user interface 30 (ofcycler 20) or user interface 186 (of bio-MEMS device 170) and thepatient or caregiver is alerted if needed. At oval 206, method 206 ends.

While network 100, one or more caregiver server computer 102 and one ormore clinician computer 110 a to 110 c are not illustrated in FIG. 9,they still may be present. And, in addition or perhaps alternatively tothe alert provided to patient P or caregiver at user interface 30 oruser interface 186, control unit 22 operates via network 100 and one ormore caregiver server computer 102 to enable a doctor or clinician atone or more clinician computer 110 a to 110 c to receive and vieweffluent white blood cell collection data, e.g., on an ongoing basis, sothat the doctor or clinician may determine if the patient has or is atrisk of developing peritonitis. The data is displayed on cliniciancomputer 110 a to 110 c in one embodiment via a dashboard of a websitefor the patient, wherein the effluent white blood cell collection datamay be presented with a flag for the clinician when it is elevated,indicating peritonitis.

It is contemplated to send effluent white blood cell collection data forpatient P after every treatment regardless of whether the data indicatesperitonitis. In this way, the doctor or clinician is able to develop apattern or profile of effluent white blood cell collection data for thepatient. It is also contemplated that the website develops a graph ortrend of effluent white blood cell collection amounts that are plottedagainst treatment dates, which is displayed upon request, for example,in addition to the dashboard. The trend as well as the dashboard in oneembodiment pinpoints or flags white blood cell collection entries thatmay indicate peritonitis or the onset thereof. A doctor or clinicianviewing multiple flagged peritonitis days is therefore able to determinewith reasonable certainty that the patient needs treatment. The whiteblood cell collection data of the second primary embodiment may bedisplayed alternatively to or in addition to the effluent temperaturedata of the first primary embodiment. Providing both blood white bloodcell collection data and effluent temperature data enables the doctor orclinician to view and analyze multiple peritonitis indicators in orderto make a medical determination for the patient.

In an alternative embodiment, bio-MEMS device 170 is located instead inpatient line 50 via a sample line and is used to analyze effluentreturning from patient P. In this manner, the bio-MEMS device may beused to sense fresh dialysis fluid delivered to the patient additionallyif desired. Or, control unit 20 may be programmed to periodically sendfresh dialysis fluid into bio-MEMS device 170 via sample port 48 ofcassette 42 and sample line 158 to sample a desired property of thefresh dialysis fluid.

Impedance Monitoring for Peritonitis

Referring now to FIGS. 11 to 13, in a third primary embodiment, animpedance monitor is used to detect peritonitis. The impedance monitoris used to look for the presence of white blood cells from the patientin the effluent fluid, which again is an indicator of peritonitis. Invarious implementations, the impedance monitor may be placed anywherethat the patient's effluent fluid may be sensed, for example, in thepatient's indwelling catheter, in the patient line or anywhere in thedrain line. In any of these locations, the catheter or line is fittedwith electrodes, e.g., in any of the ways discussed above fortemperature sensing, but with the goal now of placing electricallyconductive contacts in communication with the effluent dialysis fluidfor impedance detection.

FIG. 11 illustrates an impedance monitor 230 placed in multiplelocations. In a first location, impedance monitor 230 is placed alongthe indwelling catheter 55 of patient P, which is connected to patienttransfer set 54 and is in fluid communication with patient line 50. In asecond location (not illustrated), impedance monitor 230 is placed alongpatient line 50. In a third location (not illustrated), impedancemonitor 230 is fixed within cycler 20 and located so as to operate withdisposable cassette 42 or a line (patient line or drain line) extendingfrom disposable cassette 42. In a fifth location, impedance monitor 230is located along drain line 56 between cycler 20 and water purifier 210.In a sixth location, impedance monitor 230 is fixed within waterpurifier and is located along the drain line extending within the waterpurifier. In any of the above locations, impedance monitor 230 is ableto sense effluent fluid to detect peritonitis.

FIGS. 12 and 13 illustrate one embodiment for impedance monitor 230.FIG. 12 illustrates that in one embodiment cylindrical electrodes 240and 244 are fitted within patient line 50, the patient's indwellingcatheter 55 or drain line 56. Cylindrical electrodes 240 and 244 in theillustrated embodiment are tubular segments or sections which have anouter diameter slightly larger than the inner diameter of line 50, 56 orcatheter 55, such that electrodes 240 and 244 are press-fitted atdesired locations within line 50, 56 or catheter 55. Electrodes 240 and244 are made of an electrically conductive and medically safe material,such as stainless steel, titanium and combinations and alloys thereof.Electrodes 240 and 244 in the illustrated embodiment each include afemale port or socket 242 and 246, respectively, which is configured toreceive and hold a lead extending from the ports.

FIG. 13 illustrates that female ports or sockets 242 and 246 in oneembodiment extend through line 50, 56 or catheter 55 in such a way thatthe line or catheter wall seals around female ports or sockets 242 and246. FIG. 12 illustrates ports or sockets extending alternatively so asto be at least substantially flush with the outside of line 50, 56 orcatheter 55. In either embodiment, the outer diameter of ports orsockets 242 and 246 is larger than the hole produced in line 50, 56 orcatheter 55, such that the tube or catheter material is forced tostretch around and seal to the ports. In a further alternativeembodiment (not illustrated), ports or sockets 242 and 246 do not extendoutwardly from cylindrical electrodes 240 and 244 and the leads areinstead pierced through the line 50, 56 or catheter 55. Here, the line50, 56 or catheter 55 helps to hold the leads in place.

FIG. 13 illustrates that electrically conductive leads 248 a and 248 bextend respectively from ports or sockets 242 and 246. As with thetemperature sensing connectors of FIGS. 3 to 4B, conductive leads 248 aand 248 b of impedance monitor 230 in one embodiment extend to controlunit 22 of cycler 20 (or control unit 212 of water purifier 210),wherein the electronics and processing of the control unit causes thesignal generation and processing discussed below to be performed. In analternative embodiment (indicated by dashed lines), leads 248 a and 248b receive power from and/or carry a generated voltage to wireless module132 located along the outside of a housing 232 of impedance monitor 230.Wireless module 132 is again powered by a battery 134, such as along-lasting lithium battery, and includes electronics configured toconvert the voltage into a wireless signal and vice versa, which iscommunicated wirelessly to control unit 22 of cycler 20 in oneembodiment.

Housing 232 may have clamshell halves 234 and 236, which are hingedtogether along a living hinge discussed in connection with FIGS. 4A and4B. Housing 232 is sized to form fit over patient line 50, catheter 55or drain line 56 in the illustrated embodiment. Housing 232 isalternatively spliced between two segments of patient line 50, catheter55 or drain line 56 in a manner the same as or similar to temperaturesensing connector 120 in FIG. 3. Housing 232 in any of the aboveembodiments is made of any suitable material, such as a medical gradeplastic.

Control unit 22 (of cycler 20) or control unit 212 (of water purifier210) controlling impedance monitor 230 in one embodiment causes anelectrical frequency sweep to be generated in the effluent fluid. Thecontrol unit may include or operate with a frequency sweep generatorthat moves from a start frequency to a stop frequency at a specifiedsweep rate. It is contemplated to sweep up or down in frequency, witheither linear or logarithmic spacing. It is also contemplated to programthe control unit to sweep sine, square, pulse, ramp, triangle, orarbitrary waveforms. It is further contemplated to specify a hold time,during which the sweep remains at the stop frequency, and a return time,during which the frequency changes linearly from the stop frequency tothe start frequency.

As the impedance monitor 230 steps though the frequencies of the sweep,the resulting impedance of the effluent fluid in the indwelling catheteris measured at each different frequency. The impedances of the effluentfluid may be compared against those of fresh dialysis fluid to determineif a difference results. The impedance spectroscopy (or obtainingcomplex impedance) in one embodiment provides additional details aboutthe content(s) of the effluent fluid. For example, the electricalproperties of fibrin (normal, not indicating peritonitis) may vary fromthe electrical properties of white blood cells (indicating peritonitis).Once control unit 22 (of cycler 20) or control unit 212 (of waterpurifier 210) learns the electrical properties of different substancesthat may reside within the effluent fluid, the properties may beprogrammed into the control unit and used thereafter to determine whatif anything is entrained in the effluent dialysate stream.

FIGS. 14A and 14B illustrate example plots of impedance (Z) measured inohms (Ω) for normal patient effluent, patient effluent having whiteblood cells (indicating peritonitis), and patient effluent having otherparticulates, such as fibrin. FIG. 14A shows impedance measurements overtime, which can be continuous or discrete (on command). The exampletime-based output shows continuous data of (A) normal effluent impedance(continuous line only) and (C) effluent with increased fibrin content(dashed line), e.g., over the course of a dwell phase of a patient'speritoneal dialysis treatment. In the illustrated example, the plots forimpedance over time for effluent with normal fibrin (A) and effluentwith increased fibrin (C) start out together but then the impedance foreffluent with increased fibrin rises substantially above that ofeffluent with normal fibrin. It is expected that the curve for anepisode of peritonitis would be represented by a line extending in thearea marked (B), between that of effluent with normal fibrin (A) andeffluent with increased fibrin (C), which is confirmed in FIG. 14B. FIG.14B shows that as the patient's dwell phase proceeds, a clear differencebetween effluent with normal fibrin and effluent with increased fibrinemerges.

FIG. 14B illustrates of an impedance spectrogram corresponding to curvesillustrated in the time-based plot of FIG. 14A. The examplefrequency-based output shows continuous data of (a) normal effluentimpedance (continuous line only), (b) an episode of peritonitis resolvedby antibiotics (continuous line with boxes), and (c) effluent withincreased fibrin content (dashed line) the data at the pointshighlighted in the left frame. Spectrograms (a) to (c) cover a frequencyrange in one example of 10 Hz to 10⁶ Hz.

The example frequency-based output of FIG. 14B illustrates that there islikely to be one or more frequency range in which the impedancedifference between effluent with white blood cells (b) and the normaleffluent (a) is more starkly different than with other frequencies. InFIG. 14B, two such frequency ranges exist between f₁ and f₂ and betweenf₃ and f₄. Having multiple starkly different frequency ranges enablescontrol unit 22 or 212 to cross-check the result of one of the rangesagainst that of the other. If both or all frequency ranges indicateperitonitis, then control unit 22 or 212 (or clinician computer 110 a to110 c) outputs a determination that the patient has or is beginning toexperience peritonitis to user interface 30, user interface 220, and/orto clinician computers 110 a to 110 c via network 100 and caregiverserver computer 102. In another embodiment, control unit 22 or 212integrates the area under impedance curve (b) and compares it to anintegration of the area under impedance curve (a) to determineperitonitis or the onset thereof.

In one embodiment, curve (a) for normal effluent is determinedempirically via testing on multiple patients and then averaged todevelop standardized impedance values over the frequency sweep range.The standardized values in an embodiment are determined for each of thepopular and most frequently use glucose level peritoneal dialysis fluidsas impedance may vary based upon starting glucose levels. Thestandardized impedance values may be provided as a range that accountsfor differing dwell times, differing effluent temperatures, and otherfactors.

In another embodiment, curve (a) for normal effluent is determinedempirically, again, but here for the specific patient using system 10and cycler 20. Impedance data is taken over multiple treatments or forall treatments. A normal effluent impedance average is formed, which maybe a rolling average that may move or shift over time. It is determinedthat curve (b) for peritonitis effluent is present in one embodimentwhen the impedances in the relevant frequency ranges or averaged viaintegration are some predetermined percentage higher than thepatient-specific curve (a).

Regarding increased fibrin content curve (c), FIG. 14B illustrates thatthere is one or more specific frequency range, here between f₁ and f₂,in which the impedance of effluent having white blood cells indicatingperitonitis (b) is significantly higher than the impedance of effluenthaving increased fibrin (c). Thus, in FIG. 14B the most important rangemay be said to be between frequency range f₁ and f₂ because an increasedimpedance between frequency range f₃ and f₄ could be due either toeffluent having white blood cells indicating peritonitis (b) or effluenthaving increased fibrin (c).

It is alternatively or additionally contemplated for control unit 22 or212 (or clinician computer 110 a to 110 c) to look at the shape of theimpedance curve over the frequency range. If the shape is closest tocurve (a), control unit 22 or 212 (or clinician computer 110 a to 110 c)determines that the patient effluent is normal. If the shape is closestto curve (b), control unit 22 or 212 (or clinician computer 110 a to 110c) determines that the patient effluent shows signs of peritonitis orthe onset thereof. If the shape is closest to curve (c), control unit 22or 212 (or clinician computer 110 a to 110 c) determines that thepatient effluent has increased fibrin levels.

In any embodiment in which the impedance monitor 230 is located remotefrom cycler 20 or water purifier 210, the impedance monitor may send themeasured signals in a wired or wireless manner to the cycler forinterrogation. Impedance monitor 230 as mentioned above has the abilityto emit a frequency sweep into the effluent fluid and thus may receivepower either via battery 134 (in a wireless embodiment) or from thecycler or water purifier via power wires.

As discussed above, in an alternative embodiment, impedance monitor 230is located within cycler 20 or water purifier 210. In such case,impedance monitor 230 emits the frequency sweep into the effluent fluidby receiving power from the cycler or water purifier via power wires. Asmentioned above, impedance monitor 230 may operate with disposablecassette 42 loaded into cycler 20. Here, impedance monitor 230 mayextend through a rigid wall holding the disposable cassette sheeting inone or more places.

Control unit 22 or 212 is programmed in one embodiment to alert thepatient or caregiver at user interface 30 of cycler 20 if white bloodcells indicating peritonitis are detected. In one embodiment, even ifthe control unit evaluating the impedance sweep readings for white bloodcells is control unit 212 of water purifier 210, the audio, visual oraudiovisual alert is nevertheless provided at user interface 30 ofcycler 20 by way of a wired or wireless communication from control unit212 of water purifier 210 to control unit 22 of cycler 20 informing ofthe alert condition. In this manner, user interface 30 is the primarycommunication vehicle for a given treatment and patient P, and whereinuser interface 220 is relegated to displaying water purifier relatedinformation.

In addition or perhaps alternatively to the alert provided to patient Por caregiver at user interface 30, control unit 22 operates via network100 and one or more caregiver server computer 102 to enable a doctor orclinician at one or more clinician computer 110 a to 110 c to receiveand view the impedance obtained effluent white blood cell data, e.g., onan ongoing basis, so that the doctor or clinician may determine if thepatient has or is at risk of developing peritonitis. The data isdisplayed on clinician computer 110 a to 110 c in one embodiment via adashboard of a website for the patient, wherein the effluent white bloodcell collection data may be presented with a flag for the clinician whenit is elevated, indicating peritonitis.

It is contemplated to send the impedance obtained effluent white bloodcell data for patient P after every treatment regardless of whether thedata indicates peritonitis. In this way, the doctor or clinician is ableto develop a pattern or profile of effluent white blood cell data forthe patient. It is also contemplated that the website develops a graphor trend of effluent white blood cell amounts that are plotted againsttreatment dates, which is displayed upon request, for example, inaddition to the dashboard. The trend as well as the dashboard in oneembodiment pinpoints or flags white blood cell entries that may indicateperitonitis or the onset thereof. A doctor or clinician viewing multipleflagged peritonitis days is therefore able to determine with reasonablecertainty that the patient needs treatment. The white blood cell data ofthe third primary embodiment may be displayed alternatively to or inaddition with the white blood cell collection data of the second primaryembodiment and/or the effluent temperature data of the first primaryembodiment. Providing both white blood cell data embodiments andeffluent temperature data enables the doctor or clinician to view andanalyze multiple peritonitis indicators in order to make a medicaldetermination for the patient.

Glucose Control for Diabetes Patients

Referring now to FIGS. 15 to 20B, in a fourth primary embodiment, system10 provides a MEMS affinity glucose sensor 250, which matches or helpsto match the amount of insulin provided to patient P with an amount ofglucose delivered to the patient during treatment. FIG. 14 illustrates aversion of system 10 which uses pre-prepared PD fluid in containers orbags 94 a and 94 b instead of making PD fluid online or at the point ofuse using glucose, concentrate 84 a, buffer concentrate 84 b, orpurified water from a water purifier 210 and stored in an accumulator66, which is shown in FIGS. 1, 9, 11 and 15. In either version however,patient P receives glucose from the PD fluid. That is, the pre-preparedPD fluid in container or bags 94 a and 94 b includes glucose, which isat a level prescribed by a doctor or clinician. It should be appreciatedthat any of the primary embodiments discussed herein may be providedinstead using the pre-prepared PD fluid version of system 10 illustratedin FIG. 14.

FIG. 15 illustrates that in one pre-prepared PD fluid embodiment, aninsulin container or bag 90 is connected to the port of cassette 42 thatconnected to accumulator 66 in the point of use examples. A MEMSaffinity glucose sensor 250 is provided in drain line 56 upstream of adrain bag 96. MEMS affinity glucose sensor 250 measures the glucoselevel of the effluent dialysis fluid leaving patient P via drain line56.

FIG. 16 illustrates that in one embodiment, MEMS affinity glucose sensor250 includes a container 252 into which a sampling line 254 extends,wherein sampling line 254 may extend or tee off of drain line 56. Theeffluent sample entering container 252 of MEMS affinity glucose sensor250 first encounters a microfluidic pathway 256 that splits the glucosemolecules from the effluent fluid. The glucose molecules are thenweighed using a piezoelectric biosensor 258 in the illustratedembodiment. Piezoelectric biosensor 258 includes a cantilever 260 thatresonates with a frequency proportional to a change in the depositionrate of glucose molecules. The relation between the resonant frequencyto glucose found in the effluent fluid is illustrated below inconnection with FIG. 18. Glucose absorbed at the end of an nth PD cycleis calculated using the equation for A_(n) discussed below. Tocompensate for the absorbed glucose in the the nth PD cycle, theadministration of the insulin dosage during the subsequent n+1 PD cycleis calculated using an equation for I_(n+1) discussed below.

The MEMS affinity glucose sensor 250 in one embodiment includes theelectronics and processing to process raw signals from piezoelectricbiosensor 258 and to make a determination as to the proper concentrationof insulin to prepare with the PD solution. MEMS affinity glucose sensor250 may also include a user interface to indicate to the patient orcaregiver present during treatment that the proper insulin level isbeing determined. In alternative embodiments, either one or both of (i)electronics and processing to process raw signals from piezoelectricbiosensor 258 or (ii) the user interface for patient or caregivercommunication are provided instead by the control unit of cycler 20 orwater purifier 210 operable with the cycler.

MEMS affinity glucose sensor 250 in FIG. 15 includes wireless module 132located along the outside of the housing of device 250. Wireless module132 as discussed herein is powered by a battery 134, such as along-lasting lithium battery, and includes electronics configured toconvert the measured patient effluent glucose level into a wirelesssignal, which is sent wirelessly to control unit 22 of cycler 20 in oneembodiment. Control unit 22 of cycler 20 processes the glucose levelwireless signal and determines an amount of insulin from insulincontainer or bag 90 to deliver to heater bag 62 for the next patient PDfill. It should be noted that patient P is sometimes full of fluid fromthe previous treatment when beginning a current treatment.

The amount of insulin to deliver is based upon a desired insulinconcentration, which is correlated to the amount of glucose sensed viasensor 250 and sent to control unit 22. Knowing the desired insulinconcentration and the amount of fresh pre-prepared PD fluid from one ofcontainers or bags 92 a or 92 b to be delivered to heater bag 62, theamount of insulin to deliver from container or bag 90 to heater bag 62is determined and then pumped via fluid pump chambers 44 of disposablecassette 42 to heater bag 62. In an alternative embodiment, the amountof insulin is pumped instead from insulin container or bag 90 topre-prepared PD fluid container or bag 92 a or 92 b via fluid pumpchambers 44 of disposable cassette 42 or via a separate pump (notillustrated). An insulin port may be provided on pre-prepared PD fluidcontainer or bags 92 a and 92 b to receive the insulin.

FIG. 15 also illustrates that system 10 using MEMS affinity glucosesensor 250 in one embodiment also includes a glucose sensor 262, whichis applied, e.g., to a finger of patient P. Such glucose sensors areknown in the art in either prick or non-prick forms. In the illustratedembodiment, glucose sensor 262 outputs a glucose reading wirelessly tocontrol unit 22, control unit 212 or MEMS affinity glucose sensor 250.Wired communication between glucose sensor 262 and control unit 22,control unit 212 or MEMS affinity glucose sensor 250 is also possible.The reading(s) from glucose sensor 262 at the beginning of treatment isused in one embodiment discussed below to determine an amount of insulinto inject in a next PD fill cycle. Reading(s) from glucose sensor 262may also be used at the end of treatment to confirm that the blood sugarlevel of patient P has remained within a safe band using the glucosefeedback and insulin injection of the present disclosure. All suchinformation may also be sent to clinician computers 110 a to 110 c vianetwork 100 and one or more caregiver server computer 102.

MEMS affinity glucose sensor 250 in the point of use preparation versionin FIG. 17 is in the illustrated embodiment located within waterpurifier 210, outputs electrically to control unit 212 of the waterpurifier, and therefore does not need wireless module 132 located alongthe outside of the housing of sensor 250. Control unit 212 of waterpurifier 210 processes the glucose level signal from MEMS affinityglucose sensor 250 and determines an amount of insulin from insulincontainer or bag 90 that cycler 20 should be delivered to heater/mixingbag 62 for the next patient PD fill. It should be noted that patient Pis typically full of fluid from the previous treatment when beginning acurrent treatment. The amount of insulin to deliver is again based upona desired insulin concentration, which is correlated to the amount ofglucose sensed via device and sent to control unit 212. Knowing thedesired insulin concentration and the amount of fresh pre-prepared PDfluid that is to be mixed online and delivered to heater/mixing bag 62,the amount of insulin to deliver from container or bag 90 toheater/mixing bag 62 is determined and then pumped via fluid pumpchambers 44 of disposable cassette 42 to heater/mixing bag 62. In oneembodiment, control unit 212 of water purifier determines the amount ofinsulin to pump, sends the amount to control unit 22 of cycler 20 wiredor wirelessly, wherein control unit 22 uses the amount to command pumpchambers 44 of disposable cassette 42 to pump the desired amount ofinsulin. In another embodiment, control unit 212 relays the glucosesignal from bio-MEMS-glucose measuring device 250 to control unit 22wired or wirelessly, control unit 22 determines the amount of insulin topump and uses the amount to command pump chambers 44 of disposablecassette 42 to pump the desired amount of insulin.

Control unit 22 operates via network 100 and one or more caregiverserver computer 102 to enable a doctor or clinician at one or moreclinician computer 110 a to 110 c to view insulin usage data, e.g., on aper-treatment basis, so that the clinician may confirm that insulin isbeing delivered properly. The data is displayed in one embodiment on adashboard of a website for the patient, wherein the insulin volume andconcentration may be viewed. The data of the fourth primary embodimentmay be displayed on the doctor or clinician website for patient P incombination with the data of the first, second and/or third primaryembodiments to provide a desired combination of data. FIG. 17 alsoillustrates that system 10 using MEMS affinity glucose sensor 250 in oneembodiment also includes glucose sensor 262, which is provided and usedas described above.

Referring now to FIG. 18, method 290 summarizes one embodiment for theclosed loop insulin delivery just described. At oval 292, method 290begins. At block 294, cycler 20 actuates disposable cassette 42 to (i)pull fresh dialysis fluid (pre-prepared or made at point of use) fromheater bag 62 (pre-prepared) or heater/mixing bag 62 (point of use),along with a calculated dose of insulin from insulin bag or container 90and (ii) push the heated fresh dialysis and insulin dose fluid topatient P. At block 296, the dialysis fluid is allowed to dwell withinthe peritoneum of patient P for a doctor/clinician prescribed amount oftime. At block 298, cycler 20 actuates disposable cassette 42 to pullused dialysis fluid or effluent from the peritoneum of patient P,through patient line 50, into disposable cassette 42, and fromdisposable cassette 42, into drain line 56, to drain bag 96 (FIG. 14) ordrain 216 at water purifier 210 (FIG. 15). MEMS affinity glucose sensor250 is located somewhere along the drain line as illustrated in FIGS. 14and 15. At block 300, MEMS affinity glucose sensor 250 monitors theeffluent PD fluid for the patient's absorbed glucose amount or glucoseconcentration. At block 302, MEMS affinity glucose sensor 250 or controlunit 22 of cycler 20 or control unit 212 of water purifier 210calculates an insulin dosage based upon the glucose amount orconcentration absorbed by patient P. In an embodiment, if control unit22 of cycler 20 does not calculate the insulin dosage, then thecalculated dosage is sent to control unit 22 of cycler 20.

At diamond 304, if another cycle in the current treatment exists, thenmethod 290 returns to block 294 and control unit 22 of cycler 20provides the next patient fill using the newly calculated dose ofinsulin based upon the newly monitored amount or concentration ofglucose absorbed. At diamond 304, if another cycle in the currenttreatment does not exist, then method 290 moves to block 306 and savesthe newly calculated dose of insulin based upon the newly monitoredamount or concentration of glucose absorbed for the first fill of thenext treatment. At oval 308, method 290 ends.

It should be appreciated that method 290 applies to a PD treatment thatdoes not provide a “last fill” of fresh PD fluid that the patientcarries through the day to the next treatment (perhaps with a middayexchange). That is, patient P leaves treatment empty. When a “last fill”is provided, then method 290 after start oval 292 proceeds instead todrain block 298 to drain the “last fill” effluent fluid from thepatient, then to monitor block 300, then to calculate block 302, andthen to fill fresh fluid with insulin dose block 294. The decisiondiamond is provided instead after fill fresh fluid with insulin doseblock 294, wherein the decision is whether there is another patientdrain. If so, the modified method proceeds to dwell block 296 and backthrough blocks 298, 300, 302 and 294. When there is no additionalpatient drain, the modified method ends at oval 308. Because the firststep of the next treatment is to drain patient P, there is no need forinsulin dosage save block 306 in the “last fill” method.

FIG. 19 illustrates one example relationship between glucose absorbed inthe effluent fluid and frequency resonating from cantilever 260 ofbiosensor 258. In the example plot, effluent fluid having no absorbedglucose (continuous line) resonates at a frequency ratio of about 0.66and yields an output amplitude that is about (i) twice as much aseffluent fluid absorbed at glucose concentration×1 mg/dL (continuousline with boxes) resonating at a frequency ratio of about 0.8 and (ii)two-thirds larger than effluent fluid absorbed at glucoseconcentration×2 mg/dL (dashed line) resonating at a frequency ratio ofabout 1.0. FIG. 18 illustrates that biosensor 258 of MEMS affinityglucose sensor 250 is effective at distinguishing between differentglucose concentrations present in the effluent fluid.

In one embodiment, MEMS affinity glucose sensor 250, control unit 22 orcontrol unit 212 subtracts the glucose concentration present in theeffluent fluid from an original glucose concentration of the freshdialysis fluid delivered to patient P. The control unit is programmed todetermine the amount of glucose absorbed by the patient at the end of annth PD cycle (P_(n)) in a function as follows:

P _(n) =f(V _(n),μ,(D _(on) −D _(in))), where

-   -   n=cycle number,    -   V_(n)=volume of PD fluid delivered for the n^(th) cycle,    -   μ=a glucose absorption coefficient (a constant determined        empirically),    -   D_(on)=glucose concentration of effluent for the n^(th) cycle as        measured by MEMS affinity glucose sensor 250, and    -   D_(in)=original glucose concentration of the PD fluid for the        n^(th) cycle (PD fluids are provided in standard concentrations,        such as 0.55%, 1.5%, 2.5% and 4.25%).

Based upon the amount of glucose absorbed by the patient at the end ofthe nth PD cycle (P_(n)), the amount of insulin to provide to thepatient in the following cycle is determined in one embodiment in afunction as follows:

I _(n+1) =f(G _(I) ,P _(n) ,α,β,t), where

-   -   G_(I)=initial blood glucose level before start of therapy, which        is obtained in one embodiment from glucose sensor 262,    -   P_(n) is calculated as discussed above,    -   α and β are insulin absorption coefficients (constants        determined empirically), and t=time.

FIGS. 20A and 20B illustrate graphically how glucose levels (mg/dL) mayexceed an upper threshold when uncontrolled, but reside within doctor orclinician prescribed limits when controlled using the glucose feedbackand insulin injection of system 10 of FIGS. 15 to 18 having MEMSaffinity glucose sensor 250. As illustrated in FIG. 20A, the glucoselevel (mg/dL) in patient P rises steadily over each dwell period,passing an upper threshold in the second dwell. In FIG. 20B, however,the glucose level (mg/dL) in patient P rises during the dwell periodsbut then falls during subsequent fill phases while insulin is injectedaccording to the functions discussed above programmed into MEMS affinityglucose sensor 250, control unit 22 or control unit 212.

It should be understood that various changes and modifications to thepresently preferred embodiments described herein will be apparent tothose skilled in the art. Such changes and modifications can be madewithout departing from the spirit and scope of the present subjectmatter and without diminishing its intended advantages. It is thereforeintended that such changes and modifications be covered by the appendedclaims. For example, while the four primary embodiments have beendescribed in connection with automated peritoneal dialysis systems usingcycler 20, it is contemplated that the embodiments may also be used withmanual PD or continuous ambulatory peritoneal dialysis (“CAPD”). Also,while the MEMS biosensing for white blood sells and glucose moleculeshas been discussed in connection with a varying vibrating frequency, itis contemplated to detect other properties that may be used in atransducer to provide a sensed output property, such as voltage,including but not limited to a change in the capacitance within themicrofluidic channel, or light and a change in its frequency. Moreover,while impedance monitor 230 is illustrated and described as beingprovided with indwelling catheter 55 of patient P, it is contemplatedfor any of the four primary embodiments to be implemented with theindwelling catheter.

The invention is claimed as follows:
 1. A peritoneal dialysis (“PD”)system comprising: a cycler including a pump actuator and a control unitin operable communication with the pump actuator; a disposable setincluding a disposable cassette having a pump chamber, the disposablecassette sized and arranged to be held by the cycler such that the pumpchamber is in operable communication with the pump actuator, thedisposable set including a patient line and a drain line extending fromthe disposable cassette; a catheter for placement within a patient'speritoneal cavity and for fluid communication with the patient line; andan impedance sensor operably coupled to one of the catheter, patientline, or drain line to sense an impedance of PD fluid residing withinthe patient, or removed from the patient, the sensed impedance used todetect white blood cells to form a patient peritonitis determination,the control unit configured to communicate the peritonitisdetermination.
 2. The PD system of claim 1, wherein the sensed impedanceis sent to the control unit, and wherein the control unit is configuredto analyze the sensed impedance.
 3. The PD system of claim 2, whereinthe sensed impedance is sent to the control unit wired or wirelessly. 4.The PD system of claim 1, which includes a network and at least onedoctor or clinician computer in communication with the control unit viathe network, the control unit configured to communicate the peritonitisdetermination to at least one of a patient or caregiver via a userinterface of the cycler or the at least one doctor or clinician computervia the network.
 5. The PD system of claim 1, which includes a waterpurifier configured to supply purified water to the disposable set, thewater purifier including a water purifier control unit, wherein thesensed impedance is sent to the water purifier control unit, wherein thewater purifier control unit is configured to analyze the sensedimpedance, and wherein the cycler control unit and the water purifiercontrol unit are in communication to allow the cycler control unit tocommunicate the peritonitis determination.
 6. The PD system of claim 1,wherein the impedance sensor is located within a connector configured tocouple to the catheter, the patient line or the drain line.
 7. The PDsystem of claim 6, wherein the connector is (i) a clamshell connectorthat fits around the catheter, the patient line or the drain line or(ii) configured to be spliced between two sections of the catheter, thepatient line or the drain line.
 8. The PD system of claim 6, wherein theimpedance sensor includes electrodes positioned and arranged within thecatheter, the patient line or the drain line, the connector positionedover the electrodes.
 9. The PD system of claim 8, wherein the connectorincludes leads extending from the electrodes to (i) the control unit,(ii) a control unit of a water purifier configured to supply purifiedwater to the disposable set, or (iii) a wireless module provided withthe connector.
 10. The PD system of claim 1, which is configured toanalyze the sensed impedance of the PD fluid residing within thepatient, or removed from the patient, via a frequency sweep that movesfrom a start frequency to a stop frequency.
 11. The PD system of claim10, wherein the frequency sweep is generated by a frequency generatorprovided by or operable with the control unit.
 12. The PD system ofclaim 10, which is configured to take an impedance measurement at two ormore frequencies of the frequency sweep.
 13. The PD system of claim 10,wherein the frequency sweep enables fluid having white blood cells andresiding within the patient, or removed from the patient, to bedetermined by measuring, over at least a portion of the frequency sweep,higher impedances for the fluid having white blood cells than impedancesfor fluid not having white blood cells.
 14. The PD system of claim 13,wherein the measured impedances for fluid not having white blood cells(i) are determined based on set standard impedances or (ii) aredetermined based on impedances established for the patient.
 15. The PDsystem of claim 10, wherein the frequency sweep enables fluid havingwhite blood cells and residing within the patient, or removed from thepatient, to be distinguished from fluid having fibrin, wherein the fluidhaving fibrin yields higher impedances over at least a portion of thesweep than the fluid having white blood cells.
 16. The PD system ofclaim 1, wherein the peritonitis determination is a first peritonitisindicator, and which includes at least one different peritonitisindicator useable in combination with the first peritonitis indicator toform an overall peritonitis determination.
 17. The PD system of claim16, wherein the at least one different peritonitis indicator useable incombination with the first peritonitis indicator is obtained from atleast one of a patient effluent PD fluid temperature sensor or a whiteblood cell biosensor.
 18. The PD system of claim 1, wherein theperitonitis determination is provided in combination with insulininjection made using feedback from a patient effluent glucose biosensor.19. A peritoneal dialysis (“PD”) system comprising: a cycler including apump actuator and a control unit in operable communication with the pumpactuator; a disposable set including a pump portion sized and arrangedto be held by the cycler such that the pump portion is in operablecommunication with the pump actuator, the disposable set including apatient line and a drain line extending from the disposable cassette; acatheter for placement within a patient's peritoneal cavity and forfluid communication with the patient line; and an impedance sensoroperably coupled to one of the catheter, patient line, or drain line tosense an impedance of PD fluid residing within the patient, or removedfrom the patient, the sensed impedance used to detect white blood cellsto form a patient peritonitis determination.
 20. A peritoneal dialysis(“PD”) system comprising: a pump actuator and a control unit in operablecommunication with the pump actuator; a disposable set including a pumpportion sized and arranged to be placed in operable communication withthe pump actuator, the disposable set including a patient line and adrain line extending from the disposable cassette; a catheter forplacement within a patient's peritoneal cavity and for fluidcommunication with the patient line; and an impedance sensor operablycoupled to one of the catheter, patient line, or drain line to sense PDfluid residing within the patient, or removed from the patient, over afrequency sweep that moves from a start frequency to a stop frequency,the sensed impedance frequency sweep used to detect white blood cells toform a patient peritonitis determination.